Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

PubMed Central

Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.

2013-01-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wild-type lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an anti-mitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an anti-angiogenesis therapy such as sunitinib or sorafinib. PMID:22843210

An anthrax toxin variant with an improved activity in tumor targeting

PubMed Central

Wein, Alexander N.; Peters, Diane E.; Valivullah, Zaheer; Hoover, Benjamin J.; Tatineni, Aparna; Ma, Qian; Fattah, Rasem; Bugge, Thomas H.; Leppla, Stephen H.; Liu, Shihui

2015-01-01

Anthrax lethal toxin (LT) is an A-B type toxin secreted by Bacillus anthracis, consisting of the cellular binding moiety, protective antigen (PA), and the catalytic moiety, lethal factor (LF). To target cells, PA binds to cell-surface receptors and is then proteolytically processed forming a LF-binding competent PA oligomer where each LF binding site is comprised of three subsites on two adjacent PA monomers. We previously generated PA-U2-R200A, a urokinase-activated PA variant with LF-binding subsite II residue Arg200 mutated to Ala, and PA-L1-I210A, a matrix metalloproteinase-activated PA variant with subsite III residue Ile210 mutated to Ala. PA-U2-R200A and PA-L1-I210A displayed reduced cytotoxicity when used singly. However, when combined, they formed LF-binding competent heterogeneous oligomers by intermolecular complementation, and achieved high specificity in tumor targeting. Nevertheless, each of these proteins, in particular PA-L1-I210A, retained residual LF-binding ability. In this work, we screened a library containing all possible amino acid substitutions for LF-binding site to find variants with activity strictly dependent upon intermolecular complementation. PA-I207R was identified as an excellent replacement for the original clockwise-side variant, PA-I210A. Consequently, the new combination of PA-L1-I207R and PA-U2-R200A showed potent anti-tumor activity and low toxicity, exceeding the performance of the original combination, and warranting further investigation. PMID:26584669

Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

PubMed

Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

2015-12-01

Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

Anthrax toxin.

PubMed

Bhatnagar, R; Batra, S

2001-01-01

Anthrax is primarily a disease of herbivores caused by gram-positive, aerobic, spore-forming Bacillus anthracis. Humans are accidental hosts through the food of animal origin and animal products. Anthrax is prevelant in most parts of the globe, and cases of anthrax have been reported from almost every country. Three forms of the disease have been recognized: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). The major virulence factors of Bacillus anthracis are a poly-D glutamic acid capsule and a three-component protein exotoxin. The genes coding for the toxin and the enzymes responsible for capsule production are carried on plasmid pXO1 and pXO2, respectively. The three proteins of the exotoxin are protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). The toxins follow the A-B model with PA being the B moeity and LF/EF, the alternative A moeities. LF and EF are individually nontoxic, but in combination with PA form two toxins causing different pathogenic responses in animals and cultured cells. PA + LF forms the lethal toxin and PA + EF forms the edema toxin. During the process of intoxication, PA binds to the cell surface receptor and is cleaved at the sequence RKKR (167) by cell surface proteases such as furin generating a cell-bound, C-terminal 63 kDa protein (PA63). PA63 possesses a binding site to which LF or EF bind with high affinity. The complex is then internalized by receptor-mediated endocytosis. Acidification of the vesicle leads to instertion of PA63 into the endosomal membrane and translocation of LF/EF across the bilayer into the cytosol where they exert their toxic effects. EF has a calcium- and calmodulin-dependent adenylate cyclase activity. Recent reports indicate that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and 2), and this cleavage inactivates MAPKK1 and thus inhibits the mitogen-activated protein kinase signal transduction pathway. We describe in detail the studies so far done on unraveling the molecular mechanisms of pathogenesis of Bacillus anthracis.

Profiling lethal factor interacting proteins from human stomach using T7 phage display screening.

PubMed

Cardona-Correa, Albin; Rios-Velazquez, Carlos

2016-05-01

The anthrax lethal factor (LF) is a zinc dependent metalloproteinase that cleaves the majority of mitogen-activated protein kinase kinases and a member of NOD-like receptor proteins, inducing cell apoptosis. Despite efforts to fully understand the Bacillus anthracis toxin components, the gastrointestinal (GI) anthrax mechanisms have not been fully elucidated. Previous studies demonstrated gastric ulceration, and a substantial bacterial growth rate in Peyer's patches. However, the complete molecular pathways of the disease that results in tissue damage by LF proteolytic activity remains unclear. In the present study, to identify the profile of the proteins potentially involved in GI anthrax, protein‑protein interactions were investigated using human stomach T7 phage display (T7PD) cDNA libraries. T7PD is a high throughput technique that allows the expression of cloned DNA sequences as peptides on the phage surface, enabling the selection and identification of protein ligands. A wild type and mutant LF (E687A) were used to differentiate interaction sites. A total of 124 clones were identified from 194 interacting‑phages, at both the DNA and protein level, by in silico analysis. Databases revealed that the selected candidates were proteins from different families including lipase, peptidase‑A1 and cation transport families, among others. Furthermore, individual T7PD candidates were tested against LF in order to detect their specificity to the target molecule, resulting in 10 LF‑interacting peptides. With a minimum concentration of LF for interaction at 1 µg/ml, the T7PD isolated pepsin A3 pre‑protein (PAP) demonstrated affinity to both types of LF. In addition, PAP was isolated in various lengths for the same protein, exhibiting common regions following PRALINE alignment. These findings will help elucidate and improve the understanding of the molecular pathogenesis of GI anthrax, and aid in the development of potential therapeutic agents.

High-sensitivity MALDI-TOF MS quantification of anthrax lethal toxin for diagnostics and evaluation of medical countermeasures.

PubMed

Boyer, Anne E; Gallegos-Candela, Maribel; Quinn, Conrad P; Woolfitt, Adrian R; Brumlow, Judith O; Isbell, Katherine; Hoffmaster, Alex R; Lins, Renato C; Barr, John R

2015-04-01

Inhalation anthrax has a rapid progression and high fatality rate. Pathology and death from inhalation of Bacillus anthracis spores are attributed to the actions of secreted protein toxins. Protective antigen (PA) binds and imports the catalytic component lethal factor (LF), a zinc endoprotease, and edema factor (EF), an adenylyl cyclase, into susceptible cells. PA-LF is termed lethal toxin (LTx) and PA-EF, edema toxin. As the universal transporter for both toxins, PA is an important target for vaccination and immunotherapeutic intervention. However, its quantification has been limited to methods of relatively low analytic sensitivity. Quantification of LTx may be more clinically relevant than LF or PA alone because LTx is the toxic form that acts on cells. A method was developed for LTx-specific quantification in plasma using anti-PA IgG magnetic immunoprecipitation of PA and quantification of LF activity that co-purified with PA. The method was fast (<4 h total time to detection), sensitive at 0.033 ng/mL LTx in plasma for the fast analysis (0.0075 ng/mL LTx in plasma for an 18 h reaction), precise (6.3-9.9% coefficient of variation), and accurate (0.1-12.7%error; n ≥ 25). Diagnostic sensitivity was 100% (n = 27 animal/clinical cases). Diagnostic specificity was 100% (n = 141). LTx was detected post-antibiotic treatment in 6/6 treated rhesus macaques and 3/3 clinical cases of inhalation anthrax and as long as 8 days post-treatment. Over the course of infection in two rhesus macaques, LTx was first detected at 0.101 and 0.237 ng/mL at 36 h post-exposure and increased to 1147 and 12,107 ng/mL in late-stage anthrax. This demonstrated the importance of LTx as a diagnostic and therapeutic target. This method provides a sensitive, accurate tool for anthrax toxin detection and evaluation of PA-directed therapeutics.

Neutralization of B. anthracis toxins during ex vivo phagocytosis.

PubMed

Tarasenko, Olga; Scott, Ashley; Jones, April; Soderberg, Lee; Alusta, Pierre

2013-07-01

Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.

The Protective Antigen Component of Anthrax Toxin Forms Functional Octameric Complexes

PubMed Central

Kintzer, Alexander F.; Thoren, Katie L.; Sterling, Harry J.; Dong, Ken C.; Feld, Geoffrey K.; Tang, Iok I.; Zhang, Teri T.; Williams, Evan R.; Berger, James M.; Krantz, Bryan A.

2009-01-01

The assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. We begin to address this question using anthrax toxin as a model. The protective antigen (PA) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (LF) and edema factor (EF), to form toxic complexes. To disrupt the host, these toxic complexes are endocytosed, such that the PA oligomer forms a membrane-spanning channel that LF and EF translocate through to enter the cytosol. We show using single-channel electrophysiology that PA channels contain two populations of conductance states, which correspond with two different PA pre-channel oligomers observed by electron microscopy—the well-described heptamer and a novel octamer. Mass spectrometry demonstrates that the PA octamer binds four LFs, and assembly routes leading to the octamer are populated with even-numbered, dimeric and tetrameric, PA intermediates. Both heptameric and octameric PA complexes can translocate LF and EF with similar rates and efficiencies. Here we also report a 3.2-Å crystal structure of the PA octamer. The octamer comprises ∼20−30% of the oligomers on cells, but outside of the cell, the octamer is more stable than the heptamer under physiological pH. Thus the PA octamer is a physiological, stable, and active assembly state capable of forming lethal toxins that may withstand the hostile conditions encountered in the bloodstream. This assembly mechanism may provide a novel means to control cytotoxicity. PMID:19627991

Photoreactivation of Ultraviolet-Irradiated, Plasmid-Bearing and Plasmid-Free Strains of Bacillus anthracis

DTIC Science & Technology

1985-12-19

positive bacterium Bacillus anthracis, is a virulent and highly contagious disease to which most warm-blooded animals, including man, are susceptible... Virulent strains of B. anthracis produce a capsule composed of poly-0-glutamic acid and an exotoxin. The toxin is composed of three proteins identified...as ederma factor (EF), protective antigen (PA), and lethal factor (LF) (17). Anthrax toxin and capsule production are associated with two separate

Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R.

PubMed

Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

2016-02-25

Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2-) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R.

Charge Requirements for Proton Gradient-driven Translocation of Anthrax Toxin*

PubMed Central

Brown, Michael J.; Thoren, Katie L.; Krantz, Bryan A.

2011-01-01

Anthrax lethal toxin is used as a model system to study protein translocation. The toxin is composed of a translocase channel, called protective antigen (PA), and an enzyme, called lethal factor (LF). A proton gradient (ΔpH) can drive LF unfolding and translocation through PA channels; however, the mechanism of ΔpH-mediated force generation, substrate unfolding, and establishment of directionality are poorly understood. One recent hypothesis suggests that the ΔpH may act through changes in the protonation state of residues in the substrate. Here we report the charge requirements of LF's amino-terminal binding domain (LFN) using planar lipid bilayer electrophysiology. We found that acidic residues are required in LFN to utilize a proton gradient for translocation. Constructs lacking negative charges in the unstructured presequence of LFN translocate independently of the ΔpH driving force. Acidic residues markedly increase the rate of ΔpH-driven translocation, and the presequence is optimized in its natural acidic residue content for efficient ΔpH-driven unfolding and translocation. We discuss a ΔpH-driven charge state Brownian ratchet mechanism for translocation, where glutamic and aspartic acid residues in the substrate are the “molecular teeth” of the ratchet. Our Brownian ratchet model includes a mechanism for unfolding and a novel role for positive charges, which we propose chaperone negative charges through the PA channel during ΔpH translocation. PMID:21507946

Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death

PubMed Central

Zhu, Ping Jun; Hobson, Peyton; Southall, Noel; Qiu, Cunping; Thomas, Craig J.; Lu, Jiamo; Inglese, James; Zheng, Wei; Leppla, Stephen H.; Bugge, Thomas H.; Austin, Christopher P.; Liu, Shihui

2009-01-01

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization. PMID:19540764

Passive vaccination with a human monoclonal antibody: generation of antibodies and studies for efficacy in Bacillus anthracis infections.

PubMed

vor dem Esche, Ulrich; Huber, Maria; Zgaga-Griesz, Andrea; Grunow, Roland; Beyer, Wolfgang; Hahn, Ulrike; Bessler, Wolfgang G

2011-07-01

A major difficulty in creating human monoclonal antibodies is the lack of a suitable myeloma cell line to be used for fusion experiments. In order to create fully human monoclonal antibodies for passive immunization, the human mouse heteromyeloma cell line CB-F7 was evaluated. Using this cell line, we generated human monoclonal antibodies against Bacillus anthracis toxin components. Antibodies against protective antigen (PA) and against lethal factor (LF) were obtained using peripheral blood lymphocytes (PBLs) from persons vaccinated with the UK anthrax vaccine. PBL were fused with the cell line CB-F7. We obtained several clones producing PA specific Ig and one clone (hLF1-SAN) producing a monoclonal antibody (hLF1) directed against LF. The LF binding antibody was able to neutralize Anthrax toxin activity in an in vitro neutralization assay, and preliminary in vivo studies in mice also indicated a trend towards protection. We mapped the epitope of the antibody binding to LF by dot blot analysis and ELIFA using 80 synthetic LF peptides of 20 amino acid lengths with an overlapping range of 10 amino acids. Our results suggest the binding of the monoclonal antibody to the peptide regions 121-150 or 451-470 of LF. The Fab-fragment of the antibody hLF1 was cloned in Escherichia coli and could be useful as part of a fully human monoclonal antibody for the treatment of Anthrax infections. In general, our studies show the applicability of the CB-F7 line to create fully human monoclonal antibodies for vaccination. Copyright © 2010 Elsevier GmbH. All rights reserved.

Quantitative Determination of Lethal Toxin Proteins in Culture Supernatant of Human Live Anthrax Vaccine Bacillus anthracis A16R

PubMed Central

Zai, Xiaodong; Zhang, Jun; Liu, Ju; Liu, Jie; Li, Liangliang; Yin, Ying; Fu, Ling; Xu, Junjie; Chen, Wei

2016-01-01

Bacillus anthracis (B. anthracis) is the etiological agent of anthrax affecting both humans and animals. Anthrax toxin (AT) plays a major role in pathogenesis. It includes lethal toxin (LT) and edema toxin (ET), which are formed by the combination of protective antigen (PA) and lethal factor (LF) or edema factor (EF), respectively. The currently used human anthrax vaccine in China utilizes live-attenuated B. anthracis spores (A16R; pXO1+, pXO2−) that produce anthrax toxin but cannot produce the capsule. Anthrax toxins, especially LT, have key effects on both the immunogenicity and toxicity of human anthrax vaccines. Thus, determining quantities and biological activities of LT proteins expressed by the A16R strain is meaningful. Here, we explored LT expression patterns of the A16R strain in culture conditions using another vaccine strain Sterne as a control. We developed a sandwich ELISA and cytotoxicity-based method for quantitative detection of PA and LF. Expression and degradation of LT proteins were observed in culture supernatants over time. Additionally, LT proteins expressed by the A16R and Sterne strains were found to be monomeric and showed cytotoxic activity, which may be the main reason for side effects of live anthrax vaccines. Our work facilitates the characterization of anthrax vaccines components and establishment of a quality control standard for vaccine production which may ultimately help to ensure the efficacy and safety of the human anthrax vaccine A16R. PMID:26927174

Evaluation of clinical and serological findings for diagnosis of cutaneous anthrax infection after an outbreak.

PubMed

Gulseren, Duygu; Süzük-Yıldız, Serap; Çelebi, Bekir; Kılıç, Selçuk

2017-09-01

Anthrax, caused by the bacterium Bacillus anthracis, is one of the oldest documented infectious diseases in both livestock and humans. We aimed to evaluate clinical findings and risk factors of patients with cutaneous anthrax infection and report anti-lethal factor (LF) IgG and anti-protective antigen (PA) IgG titers in the serologic diagnosis of disease. In this study, serum samples of 18 cutaneous anthrax patients were collected and anti-LF IgG and anti-PA IgG titers were measured by enzyme-linked immunosorbent assay (ELISA). Twelve (67%) males and 6 (33%) females, with a mean age of 36.06 ± 16.58 years were included in the study. Risk factors identified in the patient population studied were slaughtering (28%), flaying (56%), chopping meat (67%), burying diseased animal corpses (17%) and milking (6%) livestock. Black eschar formation (94%), pruritus (78%) and painful lymphadenopathy (61%) were first three common clinical signs and symptoms, respectively. Fourteen (78%) patients produced a positive IgG response against PA, 11 (61%) patients produced against LF. Three (17%) patients had no response to either antigen. A detailed history of contact with sick animals or animal products along with clinical findings should be taken at the first step for the diagnosis of cutaneous anthrax infection. Serologic detection of anti-LF IgG and anti-PA IgG with ELISA may be useful auxillary method for establishing the diagnosis.

Prediction of protein-peptide interactions: application of the XPairIt API to anthrax lethal factor and substrates

NASA Astrophysics Data System (ADS)

Hurley, Margaret M.; Sellers, Michael S.

2013-05-01

As software and methodology develop, key aspects of molecular interactions such as detailed energetics and flexibility are continuously better represented in docking simulations. In the latest iteration of the XPairIt API and Docking Protocol, we perform a blind dock of a peptide into the cleavage site of the Anthrax lethal factor (LF) metalloprotein. Molecular structures are prepared from RCSB:1JKY and we demonstrate a reasonably accurate docked peptide through analysis of protein motion and, using NCI Plot, visualize and characterize the forces leading to binding. We compare our docked structure to the 1JKY crystal structure and the more recent 1PWV structure, and discuss both captured and overlooked interactions. Our results offer a more detailed look at secondary contact and show that both van der Waals and electrostatic interactions from peptide residues further from the enzyme's catalytic site are significant.

Synthesis and Biological Evaluation of Botulinum Neurotoxin A Protease Inhibitors

PubMed Central

Li, Bing; Pai, Ramdas; Cardinale, Steven C.; Butler, Michelle M.; Peet, Norton P.; Moir, Donald T.; Bavari, Sina; Bowlin, Terry L.

2010-01-01

NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogs have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC50 = 2.5 µM, FRET assay), which is 4.4-fold more potent than the lead structure, and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity. PMID:20155918

Immunization of pregnant cows with Shiga toxin-2 induces high levels of specific colostral antibodies and lactoferrin able to neutralize E. coli O157:H7 pathogenicity.

PubMed

Albanese, Adriana; Sacerdoti, Flavia; Seyahian, E Abril; Amaral, Maria Marta; Fiorentino, Gabriela; Fernandez Brando, Romina; Vilte, Daniel A; Mercado, Elsa C; Palermo, Marina S; Cataldi, Angel; Zotta, Elsa; Ibarra, Cristina

2018-03-20

E. coli O157:H7 is a foodborne pathogen responsible for bloody diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). The objective of the present work was to evaluate the ability of colostral IgG obtained from Stx2-immunized cows to prevent against E. coli O157:H7 infection and Stx2 cytotoxicity. Hyperimmune colostrum (HC) was obtained from cows intramuscularly immunized with inactivated Stx2 or vehicle for controls. Colostral IgG was purified by affinity chromatography. Specific IgG antibodies against Stx2 and bovine lactoferrin (bLF) levels in HC and the corresponding IgG (HC-IgG/bLF) were determined by ELISA. The protective effects of HC-IgG/bLF against Stx2 cytotoxicity and adhesion of E. coli O157:H7 and its Stx2-negative mutant were analyzed in HCT-8 cells. HC-IgG/bLF prevention against E. coli O157:H7 was studied in human colon and rat colon loops. Protection against a lethal dose of E. coli O157:H7 was evaluated in a weaned mice model. HC-IgG/bLF showed high anti-Stx2 titers and high bLF levels that were able to neutralize the cytotoxic effects of Stx2 in vitro and in vivo. Furthermore, HC-IgG/bLF avoided the inhibition of water absorption induced by E. coli O157:H7 in human colon and also the pathogenicity of E. coli O157:H7 and E. coli O157:H7Δstx2 in rat colon loops. Finally, HC-IgG/bLF prevented in a 100% the lethality caused by E. coli O157:H7 in a weaned mice model. Our study suggests that HC-IgG/bLF have protective effects against E. coli O157:H7 infection. These beneficial effects may be due to specific anti-Stx2 neutralizing antibodies in combination with high bLF levels. These results allow us to consider HC-IgG/bLF as a nutraceutical tool which could be used in combination with balanced supportive diets to prevent HUS. However further studies are required before recommendations can be made for therapeutic and clinical applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Peptide- and proton-driven allosteric clamps catalyze anthrax toxin translocation across membranes

PubMed Central

Das, Debasis; Krantz, Bryan A.

2016-01-01

Anthrax toxin is an intracellularly acting toxin in which sufficient information is available regarding the structure of its transmembrane channel, allowing for detailed investigation of models of translocation. Anthrax toxin, comprising three proteins—protective antigen (PA), lethal factor (LF), and edema factor—translocates large proteins across membranes. Here we show that the PA translocase channel has a transport function in which its catalytic active sites operate allosterically. We find that the phenylalanine clamp (ϕ-clamp), the known conductance bottleneck in the PA translocase, gates as either a more closed state or a more dilated state. Thermodynamically, the two channel states have >300-fold different binding affinities for an LF-derived peptide. The change in clamp thermodynamics requires distant α-clamp and ϕ-clamp sites. Clamp allostery and translocation are more optimal for LF peptides with uniform stereochemistry, where the least allosteric and least efficiently translocated peptide had a mixed stereochemistry. Overall, the kinetic results are in less agreement with an extended-chain Brownian ratchet model but, instead, are more consistent with an allosteric helix-compression model that is dependent also on substrate peptide coil-to-helix/helix-to-coil cooperativity. PMID:27506790

HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS

PubMed Central

Watson, Dennis W.

1960-01-01

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed. PMID:13783427

The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Glinert, Itai; Sittner, Assa; Kobiler, David

2012-01-01

Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T-cells. In an earlier work we demonstrated that a deletion of LF in a fully virulent strain had no effect in guinea pigs and a significant, but not major, effect in the rabbit model. These results suggested that EF might play an important role in the development of infection and mortality following exposure to B. anthracis spores. To evaluate the role of EF in B. anthracis pathogenicity we deleted the cya gene, which encodes the EF protein, in the fully virulent Vollum strain. The Δcya mutant was fully virulent in the guinea pig model as determined by LD(50) experiments. In the rabbit model, when infected subcutaneously, the absence of EF had no effect on the virulence of the mutant. However an increase of two orders of magnitude in the LD(50) was demonstrated when the rabbits were infected by intranasal instillation accompanied with partial mortality and increased mean time to death. These results argue that in the guinea pig model the presence of one of the toxins, ET or LT is sufficient for the development of the infection. In the rabbit model ET plays a role in respiratory infection, most probably mediating the early steps of host colonization. Copyright © 2011 Elsevier Ltd. All rights reserved.

Role of the α clamp in the protein translocation mechanism of anthrax toxin

PubMed Central

Brown, Michael J.; Thoren, Katie L.; Krantz, Bryan A.

2015-01-01

Membrane-embedded molecular machines are utilized to move water-soluble proteins across these barriers. Anthrax toxin forms one such machine through the self-assembly of its three component proteins—protective antigen (PA), lethal factor (LF), and edema factor (EF). Upon endocytosis into host cells, acidification of the endosome induces PA to form a membrane-inserted channel, which unfolds LF and EF and translocates them into the host cytosol. Translocation is driven by the proton motive force, comprised of the chemical potential, the proton-gradient (ΔpH), and the membrane potential (ΔΨ). A crystal structure of the lethal toxin core complex revealed an “α clamp” structure that binds to substrate helices nonspecifically. Here we test the hypothesis that through the recognition of unfolding helical structure the α clamp can accelerate the rate of translocation. We produced a synthetic PA mutant in which an α helix was crosslinked into the α clamp to block its function. This synthetic construct impairs translocation by raising a yet uncharacterized translocation barrier shown to be much less force dependent than the known unfolding barrier. We also report that the α clamp more stably binds substrates that can form helices than those, such as polyproline, that cannot. Hence the α clamp recognizes substrates by a general shape-complementarity mechanism. Substrates that are incapable of forming compact secondary structure (due to the introduction of a polyproline track) are severely deficient for translocation. Therefore, the α clamp and its recognition of helical structure in the translocating substrate play key roles in the molecular mechanism of protein translocation. PMID:26344833

Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults.

PubMed

Keitel, Wendy A; Treanor, John J; El Sahly, Hana M; Evans, Thomas G; Kopper, Scott; Whitlow, Vanessa; Selinsky, Cheryl; Kaslow, David C; Rolland, Alain; Smith, Larry R; Lalor, Peggy A

2009-08-01

VCL-AB01, a cationic lipid-formulated plasmid DNA (pDNA)-based vaccine that contains genes encoding genetically detoxified Bacillus anthracis protective antigen (PA) and lethal factor (LF), was assessed in a Phase 1, dose-escalating clinical trial in healthy adults for safety and immunogenicity, and in nonhuman primates for immunogenicity and efficacy against challenge with a lethal dose of B. anthracis spores. Healthy 18-45 year old subjects were randomly assigned to receive either the investigational vaccine containing 0.2 mg, 0.6 mg, or 2 mg of total pDNA per dose, or saline placebo, administered at 0, 1 and 2 months. The 0.2 mg and 0.6 mg dose levels were generally well tolerated; however, dose-limiting reactogenicity was observed among subjects given the first 2 mg dose and the remaining two injections in the 2 mg group were reduced to 0.6 mg. Dose-related increases in seroconversion frequencies were observed. Overall, 10%, 33.3% and 80% of subjects in the 0.2, 0.6 and 2 mg groups, respectively, developed antibodies to PA and/or LF as measured by ELISA; however, antibodies with toxin neutralizing activity (TNA) were detected in only one subject. In monkeys that received a 0.6 mg dose three times at 2 week intervals, low levels of antibodies were detected by ELISA but not by the TNA assay in all animals just prior to challenge. Despite the absence of TNA, 75% animals survived the lethal challenge. In summary, VCL-AB01 was generally well tolerated in humans at a dose that provided immunity in monkeys despite the lack of robust TNA titers in either species.

Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

PubMed

Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

2017-03-01

The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B 7 ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B 7 components of C2 toxin and LT, C2IIa and PA 63 , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA 63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA 63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA 63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA 63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.

PubMed

Fasanella, A; Tonello, F; Garofolo, G; Muraro, L; Carattoli, A; Adone, R; Montecucco, C

2008-10-23

In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.

Peptide probes reveal a hydrophobic steric ratchet in the anthrax toxin protective antigen translocase

PubMed Central

Colby, Jennifer M.; Krantz, Bryan A.

2015-01-01

Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor (LF) and edema factor (EF), into the host cytosol under the proton motive force (PMF). Protein translocation under a PMF is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between LF amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides; and while these steric interactions may make a peptide translocate poorly, in the context of folded domains they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. PMID:26363343

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species.

PubMed

Acosta-Smith, Erika; Viveros-Jiménez, Karina; Canizalez-Román, Adrian; Reyes-Lopez, Magda; Bolscher, Jan G M; Nazmi, Kamran; Flores-Villaseñor, Hector; Alapizco-Castro, Gerardo; de la Garza, Mireya; Martínez-Garcia, Jesús J; Velazquez-Roman, Jorge; Leon-Sicairos, Nidia

2017-01-01

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species.

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species

PubMed Central

Acosta-Smith, Erika; Viveros-Jiménez, Karina; Canizalez-Román, Adrian; Reyes-Lopez, Magda; Bolscher, Jan G. M.; Nazmi, Kamran; Flores-Villaseñor, Hector; Alapizco-Castro, Gerardo; de la Garza, Mireya; Martínez-Garcia, Jesús J.; Velazquez-Roman, Jorge; Leon-Sicairos, Nidia

2018-01-01

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species. PMID:29375503

Factors Affecting Lactoferrin Concentration in Human Milk: How Much Do We Know?

PubMed Central

Villavicencio, Aasith; Rueda, Maria S.; Turin, Christie G.; Ochoa, Theresa J.

2017-01-01

Lactoferrin (LF) is a breast milk glycoprotein with antimicrobial and anti-inflammatory effects. Its beneficial properties in infants, especially in those born preterm, are currently being studied in clinical trials. However, the maternal and nursing infant factors that may affect the concentration of LF in breast milk are still not clear. We conducted a systematic review to investigate the factors that may affect LF concentration. We used a 2-step approach to identify the eligible studies according to inclusion/exclusion criteria and to determine which studies would be considered. We included 70 qualified articles from 29 countries with publication dates ranging from 1976 to 2015. We described the correlation between LF concentration in breast milk and lactation stage; 10 maternal factors, such as race, parity, among others; and 2 infant factors, infections and prematurity. Colostrum has the highest LF levels, but they decrease with days postpartum. No other factor has been consistently associated with LF concentration. A major limitation of the majority of the published studies is the small sample size and the different methods used to measure LF concentration. Therefore, there is a need for large, multicenter studies with standardized study design, sample collection, and LF measurement methods to identify clinically significant factors associated with LF expression in breast milk, which will help promote exclusive breastfeeding in preterm infants. PMID:28075610

Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.

PubMed

Saito, Takeyuki; Yokota, Kazuya; Kobayakawa, Kazu; Hara, Masamitsu; Kubota, Kensuke; Harimaya, Katsumi; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Matsumoto, Yoshihiro; Doi, Toshio; Shiba, Keiichiro; Nakashima, Yasuharu; Okada, Seiji

2017-01-01

Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.

Lactobacillus fermentum Suo Attenuates HCl/Ethanol Induced Gastric Injury in Mice through Its Antioxidant Effects

PubMed Central

Suo, Huayi; Zhao, Xin; Qian, Yu; Sun, Peng; Zhu, Kai; Li, Jian; Sun, Baozhong

2016-01-01

The purpose of the study was to determine the inhibitory effects of Lactobacillus fermentum Suo (LF-Suo) on HCl/ethanol induced gastric injury in ICR (Institute for Cancer Research) mice and explain the mechanism of these effects through the molecular biology activities of LF-Suo. The studied mice were divided into four groups: healthy, injured, LF-Suo-L and LF-Suo-H group. After the LF-Suo intragastric administration, the gastric injury area was reduced compared to the injured group. The serum MOT (motilin), SP (substance P), ET (endothelin) levels of LF-Suo treated mice were lower, and SS (somatostatin), VIP (vasoactive intestinal peptide) levels were higher than the injured group mice. The cytokine IL-6 (interleukin 6), IL-12 (interleukin 12), TNF-α (tumor necrosis factor-α) and IFN-γ (interferon-γ) serum levels were decreased after the LF-Suo treatment. The gastric tissues SOD (superoxide dismutase), GSH-Px (glutathione peroxidase), NO (nitric oxide) and activities of LF-Suo treated mice were increased and MDA (malondialdehyde) activity was decreased compared to the injured group mice. By the RT-PCR assay, LF-Suo raised the occludin, EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), Fit-1 (fms-like tyrosine kinase-1), IκB-α (inhibitor kappaB-α), nNOS (neuronal nitric oxide synthase), eNOS (endothelial nitric oxide synthase), Mn-SOD, Cu/Zn-SOD, CAT (catalase) mRNA or protein expressions and reduced the COX-2, NF-κB (nuclear factor kappaB), and iNOS (inducible nitric oxide synthase) expressions in gastric tissues compared to the gastric injured group mice. A high concentration (1.0 × 109 CFU/kg b.w.) of LF-Suo treatment showed stronger anti-gastric injury effects compared to a low concentration of (0.5 × 109 CFU/kg b.w.) of LF-Suo treatment. LF-Suo also showed strong survival in pH 3.0 man-made gastric juice and hydrophobic properties. These results indicate that LF-Suo has potential use as probiotics for its gastric injury treatment effects. PMID:26978395

Advanced Vaccine Candidates for Lassa Fever

PubMed Central

Lukashevich, Igor S.

2012-01-01

Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered. PMID:23202493

Advanced vaccine candidates for Lassa fever.

PubMed

Lukashevich, Igor S

2012-10-29

Lassa virus (LASV) is the most prominent human pathogen of the Arenaviridae. The virus is transmitted to humans by a rodent reservoir, Mastomys natalensis, and is capable of causing lethal Lassa Fever (LF). LASV has the highest human impact of any of the viral hemorrhagic fevers (with the exception of Dengue Fever) with an estimated several hundred thousand infections annually, resulting in thousands of deaths in Western Africa. The sizeable disease burden, numerous imported cases of LF in non-endemic countries, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Presently there is no licensed vaccine against LF or approved treatment. Recently, several promising vaccine candidates have been developed which can potentially target different groups at risk. The purpose of this manuscript is to review the LASV pathogenesis and immune mechanisms involved in protection. The current status of pre-clinical development of the advanced vaccine candidates that have been tested in non-human primates will be discussed. Major scientific, manufacturing, and regulatory challenges will also be considered.

Identification of the cellular receptor for anthrax toxin

NASA Astrophysics Data System (ADS)

Bradley, Kenneth A.; Mogridge, Jeremy; Mourez, Michael; Collier, R. John; Young, John A. T.

2001-11-01

The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.

Plasmids encoding therapeutic agents

DOEpatents

Keener, William K [Idaho Falls, ID

2007-08-07

Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

Lactoferrin and prematurity: a promising milk protein?

PubMed

Ochoa, Theresa J; Sizonenko, Stéphane V

2017-02-01

Lactoferrin (Lf) is the major whey protein in milk, with multiple beneficial health effects including direct antimicrobial activities, anti-inflammatory effects, and iron homeostasis. Oral Lf supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury, bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors, and decreased inflammation. It also supported brain development and cognition. Further, Lf can prevent preterm delivery by reducing proinflammatory factors and inhibiting premature cervix maturation. We review here the latest research on Lf in the field of neonatology.

Comparative analysis of virulence traits between a Legionella feeleii strain implicated in Pontiac fever and a strain that caused Legionnaires' disease.

PubMed

Wang, Changle; Saito, Mitsumasa; Tanaka, Tamami; Amako, Kazunobu; Yoshida, Shin-ichi

2015-12-01

Legionella strains of the same species and serogroup are known to cause Legionnaires' disease (a potentially fatal atypical pneumonia) or Pontiac fever (a mild, flu-like disease), but the bacterial factors that define these dramatic differences in pathology have not been elucidated. To gain a better understanding of these factors, we compared the characteristics of Legionella feeleii strains that were isolated from either a sample of freshwater implicated in an outbreak of Pontiac fever (ATCC 35072, serogroup 1, LfPF), or a patient with Legionnaires' disease (ATCC 38549, serogroup 2, LfLD). Growth of LfPF and LfLD in BYE broth was slower than the positive control, Legionella pneumophila strain JR32. However, LfLD grew faster than LfPF at 42 °C. After in vitro infection to J774 murine or U937 human macrophage cell lines and A549 human lung epithelial cell line, LfLD showed a higher cell infection rate, stronger internalization by host cells, and greater cytotoxicity than that of LfPF. Large amounts of IL-6 and IL-8 were secreted by human host cells after infection with LfLD, but not with LfPF. LfLD possessed mono-polar flagellum while LfPF was unflagellated. When LfLD was cultured at 25, 30 and 37 °C, the bacteria had higher motility rate at lower temperatures. Based on our results, this is the first study that showed distinct characteristics between LfPF and LfLD, which may give important leads in elucidating differences in their virulence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Macrophage Infiltration Is a Causative Factor for Ligamentum Flavum Hypertrophy through the Activation of Collagen Production in Fibroblasts.

PubMed

Saito, Takeyuki; Hara, Masamitsu; Kumamaru, Hiromi; Kobayakawa, Kazu; Yokota, Kazuya; Kijima, Ken; Yoshizaki, Shingo; Harimaya, Katsumi; Matsumoto, Yoshihiro; Kawaguchi, Kenichi; Hayashida, Mitsumasa; Inagaki, Yutaka; Shiba, Keiichiro; Nakashima, Yasuharu; Okada, Seiji

2017-12-01

Ligamentum flavum (LF) hypertrophy causes lumbar spinal canal stenosis, leading to leg pain and disability in activities of daily living in elderly individuals. Although previous studies have been performed on LF hypertrophy, its pathomechanisms have not been fully elucidated. In this study, we demonstrated that infiltrating macrophages were a causative factor for LF hypertrophy. Induction of macrophages into the mouse LF by applying a microinjury resulted in LF hypertrophy along with collagen accumulation and fibroblasts proliferation at the injured site, which were very similar to the characteristics observed in the severely hypertrophied LF of human. However, we found that macrophage depletion by injecting clodronate-containing liposomes counteracted LF hypertrophy even with microinjury. For identification of fibroblasts in the LF, we used collagen type I α 2 linked to green fluorescent protein transgenic mice and selectively isolated green fluorescent protein-positive fibroblasts from the microinjured LF using laser microdissection. A quantitative RT-PCR on laser microdissection samples revealed that the gene expression of collagen markedly increased in the fibroblasts at the injured site with infiltrating macrophages compared with the uninjured location. These results suggested that macrophage infiltration was crucial for LF hypertrophy by stimulating collagen production in fibroblasts, providing better understanding of the pathophysiology of LF hypertrophy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Erythropoietin and Nrf2: key factors in the neuroprotection provided by apo-lactoferrin.

PubMed

Zakharova, E T; Sokolov, A V; Pavlichenko, N N; Kostevich, V A; Abdurasulova, I N; Chechushkov, A V; Voynova, I V; Elizarova, A Yu; Kolmakov, N N; Bass, M G; Semak, I V; Budevich, A I; Kozhin, P M; Zenkov, N K; Klimenko, V M; Kirik, O V; Korzhevskii, D E; Menshchikova, E B; Vasilyev, V B

2018-05-10

Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs. Other researchers showed that EPO can act as a protectant against severe brain injury and status epilepticus in rats. Therefore, we tried rhLF as a protector against the severe neurologic disorders developed in rats, such as the rotenone-induced model of Parkinson's disease and experimental autoimmune encephalomyelitis as a model of multiple sclerosis, and observed its capacity to mitigate the grave symptoms. Moreover, an intraperitoneal injection of rhLF into mice 1 h after occlusion of the medial cerebral artery significantly diminished the necrosis area measured on the third day in the ischaemic brain. During this period EPO was synthesized in various murine tissues. It was known that EPO induces nuclear translocation of Nrf2, which, like HIF-1-alpha, is a transcription factor. In view that under conditions of hypoxia both factors demonstrate a synergistic protective effect, we suggested that LF activates the Keap1/Nrf2 signaling pathway, an important link in proliferation and differentiation of normal and malignant cells. J774 macrophages were cultured for 3 days without or in the presence of ferric and ferrous ions (RPMI-1640 and DMEM/F12, respectively). Then cells were incubated with rhLF or Deferiprone. Confocal microscopy revealed nuclear translocation of Nrf2 (the key event in Keap1/Nrf2 signaling) induced by apo-rhLF (iron-free, RPMI-1640). The reference compound Deferiprone (iron chelator) had the similar effect. Upon iron binding (in DMEM/F12) rhLF did not activate the Keap1/Nrf2 pathway. Added to J774, apo-rhLF enhanced transcription of Nrf2-dependent genes coding for glutathione S-transferase P and heme oxygenase-1. Western blotting revealed presence of Nrf2 in mice brain after 6 days of oral administration of apo-rhLF, but not Fe-rhLF or equivalent amount of PBS. Hence, apo-LF, but not holo-LF, induces the translocation of Nrf2 from cytoplasm to the nucleus, probably due to its capacity to induce EPO synthesis.

Leptin-induced inflammation by activating IL-6 expression contributes to the fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis.

PubMed

Sun, Chao; Wang, Zhen; Tian, Ji-Wei; Wang, Yun-Hao

2018-04-27

The ongoing chronic inflammation and subsequent fibrosis play an important role in ligamentum flavum (LF) fibrosis and hypertrophy in patients with lumbar spinal canal stenosis (LSCS). Leptin is a chronic inflammatory mediator and involved in the fibrotic process in multiple organ systems. The present study aimed to investigate the role of leptin in LF fibrosis and its related regulatory mechanisms. The LF specimens were obtained during the surgery from 12 patients with LSCS (LSCS group) and 12 control patients with lumbar disc herniation (LDH) group. The morphologic changes and fibrosis score of LF were assessed by Hematoxylin and eosin (H&E) and Masson's trichrome staining respectively. The location and expression of leptin in LF tissues were determined. Then, the LF cells were cultured and exposed to recombinant human leptin (rhleptin). Collagen I and III were used as fibrosis markers and IL-6 was used as the inflammatory factor. As a result, the LF thickness and fibrosis score in the LSCS group were significantly higher than those in the LDH group ( P <0.05). Leptin was detected in the hypertrophied LF and its expression was substantially increased in the LSCS group and positively correlated with LF thickness and fibrosis score ( P <0.05). Moreover, our in vitro experiments revealed that rhleptin treated LF cells elevated the expression of collagen I and III. Finally, leptin administration induced IL-6 expression via nuclear factor-κB (NF-κB) pathway in LF cell ( P <0.05). Our study demonstrated novel molecular events for leptin-induced inflammation in LF tissue by promoting IL-6 expression and thus might have potential implications for clarifying the mechanism underlying LF fibrosis and hypertrophy. © 2018 The Author(s).

A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

PubMed

Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

2017-05-22

Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to improve implementation outcomes. Successfully achieving this requires undertaking formative research on the possible constraining and inhibiting factors, and incorporating the findings in the design and implementation of MDA for LF.

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection

PubMed Central

Ibekwe, Titus S.; Nwegbu, Maxwell M.; Asogun, Daniel; Adomeh, Donatus I.; Okokhere, Peter O.

2012-01-01

Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case–control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF “rapid screening kit” since RT-PCR is unavailable in most centers. In the interim, “high clinical index of suspicion,” irrespective of IgM status, requires urgent referral to confirmatory centers. PMID:23661877

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection.

PubMed

Ibekwe, Titus S; Nwegbu, Maxwell M; Asogun, Daniel; Adomeh, Donatus I; Okokhere, Peter O

2012-10-01

Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. A prospective case-control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF "rapid screening kit" since RT-PCR is unavailable in most centers. In the interim, "high clinical index of suspicion," irrespective of IgM status, requires urgent referral to confirmatory centers.

Electrostatic Ratchet in the Protective Antigen Channel Promotes Anthrax Toxin Translocation*

PubMed Central

Wynia-Smith, Sarah L.; Brown, Michael J.; Chirichella, Gina; Kemalyan, Gigi; Krantz, Bryan A.

2012-01-01

Central to the power-stroke and Brownian-ratchet mechanisms of protein translocation is the process through which nonequilibrium fluctuations are rectified or ratcheted by the molecular motor to transport substrate proteins along a specific axis. We investigated the ratchet mechanism using anthrax toxin as a model. Anthrax toxin is a tripartite toxin comprised of the protective antigen (PA) component, a homooligomeric transmembrane translocase, which translocates two other enzyme components, lethal factor (LF) and edema factor (EF), into the cytosol of the host cell under the proton motive force (PMF). The PA-binding domains of LF and EF (LFN and EFN) possess identical folds and similar solution stabilities; however, EFN translocates ∼10–200-fold slower than LFN, depending on the electrical potential (Δψ) and chemical potential (ΔpH) compositions of the PMF. From an analysis of LFN/EFN chimera proteins, we identified two 10-residue cassettes comprised of charged sequence that were responsible for the impaired translocation kinetics of EFN. These cassettes have nonspecific electrostatic requirements: one surprisingly prefers acidic residues when driven by either a Δψ or a ΔpH; the second requires basic residues only when driven by a Δψ. Through modeling and experiment, we identified a charged surface in the PA channel responsible for charge selectivity. The charged surface latches the substrate and promotes PMF-driven transport. We propose an electrostatic ratchet in the channel, comprised of opposing rings of charged residues, enforces directionality by interacting with charged cassettes in the substrate, thereby generating forces sufficient to drive unfolding. PMID:23115233

Increased sorbitol levels in the hypertrophic ligamentum flavum of diabetic patients with lumbar spinal canal stenosis.

PubMed

Luo, Jiaquan; Huang, Lu; Chen, Zhuo; Zeng, Zhaoxun; Miyamoto, Takeshi; Wu, Hao; Zhang, Zhongzu; Pan, Zhimin; Fujita, Nobuyuki; Hikata, Tomohiro; Iwanami, Akio; Tsuji, Takashi; Ishii, Ken; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Cao, Kai

2017-05-01

The pathomechanism of the ligamentum flavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear. A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in these patients. Twenty-four diabetic and 20 normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemical methods, and the levels of sorbitol, pro-inflammatory cytokines, and the fibrogenic factor, TGF-β1, in the LF were analyzed. In vitro experiments were performed using NIH3T3 fibroblasts to evaluate the effect of high-glucose conditions and an aldose reductase inhibitor on the cellular production of sorbitol, pro-inflammatory factors, and TGF-β1. We found that the LF of diabetic patients exhibited significantly higher levels of sorbitol and pro-inflammatory cytokines, TGF-β1 and of CD68-positive staining than that of the normoglycemic subjects. The diabetic LF was significantly thicker than that of the controls, and showed evidence of degeneration. The high glucose-cultured fibroblasts exhibited significantly higher levels of sorbitol, pro-inflammatory factors, and TGF-β1 compared to the low glucose-cultured cells, and these levels were dose-dependently reduced by treatment with the aldose reductase inhibitor. Taken together, our data suggests that increased sorbitol levels in the LF of diabetic patients results in increased production of pro-inflammatory and fibrogenic factor, which contribute to LF hypertrophy, and could increase the susceptibility of diabetic patients to LSCS. Furthermore, aldose reductase inhibition effectively reduced the levels of sorbitol and sorbitol-induced pro-inflammatory factor expression in high glucose-cultured fibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1058-1066, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Measuring teamwork and conflict among emergency medical technician personnel.

PubMed

Patterson, P Daniel; Weaver, Matthew D; Weaver, Sallie J; Rosen, Michael A; Todorova, Gergana; Weingart, Laurie R; Krackhardt, David; Lave, Judith R; Arnold, Robert M; Yealy, Donald M; Salas, Eduardo

2012-01-01

We sought to develop a reliable and valid tool for measuring teamwork among emergency medical technician (EMT) partnerships. We adapted existing scales and developed new items to measure components of teamwork. After recruiting a convenience sample of 39 agencies, we tested a 122-item draft survey tool (EMT-TEAMWORK). We performed a series of exploratory factor analyses (EFAs) and confirmatory factor analysis (CFA) to test reliability and construct validity, describing variation in domain and global scores using descriptive statistics. We received 687 completed surveys. The EFAs identified a nine-factor solution. We labeled these factors 1) Team Orientation, 2) Team Structure & Leadership, 3) Partner Communication, Team Support, & Monitoring, 4) Partner Trust and Shared Mental Models, 5) Partner Adaptability & Back-Up Behavior, 6) Process Conflict, 7) Strong Task Conflict, 8) Mild Task Conflict, and 9) Interpersonal Conflict. We tested a short-form (30-item SF) and long-form (45-item LF) version. The CFAs determined that both the SF and the LF possess positive psychometric properties of reliability and construct validity. The EMT-TEAMWORK-SF has positive internal consistency properties, with a mean Cronbach's alpha coefficient ≥0.70 across all nine factors (mean = 0.84; minimum = 0.78, maximum = 0.94). The mean Cronbach's alpha coefficient for the EMT-TEAMWORK-LF was 0.87 (minimum = 0.79, maximum = 0.94). There was wide variation in weighted scores across all nine factors and the global score for the SF and LF. Mean scores were lowest for the Team Orientation factor (48.1, standard deviation [SD] 21.5, SF; 49.3, SD 19.8, LF) and highest (more positive) for the Interpersonal Conflict factor (87.7, SD 18.1, for both SF and LF). We developed a reliable and valid survey to evaluate teamwork between EMT partners.

Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis.

PubMed

Hirata, Marina; Ishigami, Masatoshi; Matsushita, Yoshihiro; Ito, Takanori; Hattori, Hisashi; Hibi, Hideharu; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

2016-10-01

: Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl 4 )-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-α, IL-1β, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl 4 -induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF-depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl 4 -induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF. This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced differentiation of tissue-repairing macrophages expressing high levels of the profibrinolytic factor matrix metalloproteinase 13. Furthermore, hepatocyte growth factor played a central role in the SHED-CM-mediated resolution of LF. This is the first report demonstrating the multifaceted therapeutic benefits of secreted factors derived from SHEDs for LF. ©AlphaMed Press.

Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes.

PubMed

Ishii, Nanase; Ryu, Mizuyuki; Suzuki, Yasushi A

2017-02-01

The aim of this study was to evaluate the effect of bovine lactoferrin (bLf) on melanin-producing cells and to elucidate its mechanism of action. We tested the anti-melanogenic effect of bLf on a 3-dimensional cultured pigmentation skin model and confirmed a 20% reduction in pigmentation, suggesting that bLf was transdermally absorbed and it suppressed melanin production. Treatment of human melanoma cells with bLf resulted in a significant, dose-dependent suppression of melanin production. Apo-bLf and holo-bLf suppressed melanogenesis to the same degree as bLf. The key feature behind this anti-melanogenic effect of bLf was the down-regulation of the microphthalmia-associated transcription factor (MITF), leading to the suppression of tyrosinase activity. Treatment with bLf resulted in both decreased expression of MITF mRNA and enhanced degradation of MITF protein. However, the primary effector was enhanced phosphorylation of extracellular signal-regulated kinase (ERK), leading to the phosphorylation and degradation of MITF. Our finding that bLf suppresses melanin production in melanocytes indicates that bLf is a possible candidate for application as a skin-whitening agent.

Evaluation of the bioactivity of recombinant human lactoferrins toward murine osteoblast-like cells for bone tissue engineering.

PubMed

Amini, Ashley A; Nair, Lakshmi S

2013-05-01

Lactoferrin (LF), which belongs to the iron-binding transferrin family, is an important regulator of the levels of free iron in the body fluids. LF has raised significant interest as a bioactive protein due to its wide array of physiological effects on many different cell types, including osteoblasts and osteoclasts. The glycoprotein's degree of iron saturation has a pivotal influence on its physical structure. The objective of this study is to investigate the biological effects of apo (low iron saturation), pis (partially iron saturated), and holo (high iron saturation) recombinant human LF (rhLF) on MC3T3-E1 cells to identify the suitable candidate for bone tissue engineering application. Our studies demonstrated a dose-dependent mitogenic response of MC3T3 to rhLF treatment irrespective of the iron concentration. Furthermore, rhLF induced the cells to produce transcription factors, chemokines, and cytokines as determined by β-catenin activation, phosphorylation of Akt, vascular endothelial growth factor, and interleukin (IL-6) expression. The iron saturation of rhLF did not have any significant effect on these biological activities of MC3T3 cells. In addition, the overall pattern of gene regulation in MC3T3-E1 cells upon rhLF treatment was followed by a global microarray analysis. Among the 45,200 genes tested, only 251 genes were found to be regulated by rhLFs of different iron concentrations. Of these, the transferrin receptor (Tfrc) was the only gene differentially regulated by the iron saturated and iron depleted (apo) rhLFs. In conclusion, the study demonstrated that rhLF is a bioactive protein and that the iron saturation of rhLF may not play a significant role in modulating osteoblast functions.

Effect of bovine apo-lactoferrin on the growth and virulence of Actinobacillus pleuropneumoniae.

PubMed

Luna-Castro, Sarahí; Aguilar-Romero, Francisco; Samaniego-Barrón, Luisa; Godínez-Vargas, Delfino; de la Garza, Mireya

2014-10-01

Actinobacillus pleuropneumoniae (App) is a Gram-negative bacterium that causes porcine pleuropneumonia, leading to economic losses in the swine industry. Due to bacterial resistance to antibiotics, new treatments for this disease are currently being sought. Lactoferrin (Lf) is an innate immune system glycoprotein of mammals that is microbiostatic and microbicidal and affects several bacterial virulence factors. The aim of this study was to investigate whether bovine iron-free Lf (BapoLf) has an effect on the growth and virulence of App. Two serotype 1 strains (reference strain S4074 and the isolate BC52) and a serotype 7 reference strain (WF83) were analyzed. First, the ability of App to grow in iron-charged BLf was discarded because in vivo, BapoLf sequesters iron and could be a potential source of this element favoring the infection. The minimum inhibitory concentration of BapoLf was 14.62, 11.78 and 10.56 µM for the strain BC52, S4074 and WF83, respectively. A subinhibitory concentration (0.8 µM) was tested by assessing App adhesion to porcine buccal epithelial cells, biofilm production, and the secretion and function of toxins and proteases. Decrease in adhesion (24-42 %) was found in the serotype 1 strains. Biofilm production decreased (27 %) for only the strain 4074 of serotype 1. Interestingly, biofilm was decreased (60-70 %) in the three strains by BholoLf. Hemolysis of erythrocytes and toxicity towards HeLa cells were not affected by BapoLf. In contrast, proteolytic activity in all strains was suppressed in the presence of BapoLf. Finally, oxytetracycline produced synergistic effect with BapoLf against App. Our results suggest that BapoLf affects the growth and several of the virulence factors in App.

Protection of SK-N-MC cells against β-amyloid peptide-induced degeneration using neuron growth factor-loaded liposomes with surface lactoferrin.

PubMed

Kuo, Yung-Chih; Wang, Cheng-Ting

2014-07-01

A liposomal system with surface lactoferrin (Lf) was developed for delivering neuron growth factor (NGF) across the blood-brain barrier (BBB) and improving the viability of neuron-like SK-N-MC cells with deposited β-amyloid peptide (Aβ). The Lf-grafted liposomes carrying NGF (Lf/NGF-liposomes) were applied to a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to fibrillar Aβ1-42-insulted SK-N-MC cells. An increase in cholesterol mole percentage enhanced the particle size, absolute value of zeta potential, and physical stability, however, reduced the entrapment efficiency and release rate of NGF. In addition, an increase in Lf concentration increased the particle size, surface nitrogen percentage, NGF permeability across the BBB, and viability of HBMECs, HAs, and SK-N-MC cells, however, decreased the absolute value of zeta potential, surface phosphorus percentage, and loading efficiency of Lf. After treating with Lf/NGF-liposomes, a higher Aβ concentration yielded a lower survival of SK-N-MC cells. The current Lf/NGF-liposomes are efficacious drug carriers to target the BBB and inhibit the Aβ-induced neurotoxicity as potential pharmacotherapy for Alzheimer's disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

A preliminary study of the effects of an extract of Ligularia fischeri leaves on type II collagen-induced arthritis in DBA/1J mice.

PubMed

Choi, Eun Mi; Kim, Young Ho

2008-01-01

The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.

Measuring teamwork and conflict among Emergency Medical Technician personnel

PubMed Central

Patterson, P. Daniel; Weaver, Matthew D.; Weaver, Sallie J.; Rosen, Michael A.; Todorova, Gergana; Weingart, Laurie R.; Krackhardt, David; Lave, Judith R.; Arnold, Robert M.; Yealy, Donald M.; Salas, Eduardo

2011-01-01

Objective We sought to develop a reliable and valid tool for measuring teamwork among Emergency Medical Technician (EMT) partnerships. Methods We adapted existing scales and developed new items to measure components of teamwork. After recruiting a convenience sample of 39 agencies, we tested a 122-item draft survey tool. We performed a series of Exploratory Factor Analyses (EFA) and Confirmatory Factor Analysis (CFA) to test reliability and construct validity, describing variation in domain and global scores using descriptive statistics. Results We received 687 completed surveys. The EFA analyses identified a 9-factor solution. We labeled these factors [1] Team Orientation, [2] Team Structure & Leadership, [3] Partner Communication, Team Support, & Monitoring, [4] Partner Trust and Shared Mental Models, [5] Partner Adaptability & Back-Up Behavior, [6] Process Conflict, [7] Strong Task Conflict, [8] Mild Task Conflict, and [9] Interpersonal Conflict. We tested a short form (30-item SF) and long form (45-item LF) version. The CFA analyses determined that both the SF and LF versions possess positive psychometric properties of reliability and construct validity. The EMT-TEAMWORK-SF has positive internal consistency properties with a mean Cronbach’s alpha coefficient ≥0.70 across all 9-factors (mean=0.84; min=0.78, max=0.94). The mean Cronbach’s alpha coefficient for the EMT-TEAMWORK-LF version was 0.87 (min=0.79, max=0.94). There was wide variation in weighted scores across all 9 factors and the global score for the SF and LF versions. Mean scores were lowest for the Team Orientation factor (48.1, SD 21.5 SF; 49.3 SD 19.8 LF) and highest (more positive) for the Interpersonal Conflict factor (87.7 SD 18.1 for both SF and LF). Conclusions We developed a reliable and valid survey to evaluate teamwork between EMT partners. PMID:22128909

Monitoring the kinetics of the pH driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance

PubMed Central

Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; Mcginn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E. P.; Pentelute, B. L.; Collier, R. John; Fisher, Mark T.

2013-01-01

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å beta barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor (EF), from the endosome into the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance (SPR) and bio-layer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from pH 7.5 to pH 5.0, mirroring acidification of the endosome. Once transitioned, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto EM grids, where the PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early or late endosomal pH conditions (5.5 to 5.0 respectively). Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions. PMID:23964683

Monitoring the kinetics of the pH-driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance.

PubMed

Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; McGinn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E P; Pentelute, B L; Collier, R John; Fisher, Mark T

2013-09-17

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å β barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH-dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor, from the endosome to the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance and biolayer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from 7.5 to 5.0, mirroring acidification of the endosome. Once it had undergone the transition, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto electron microscopy grids, where PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early (pH 5.5) or late (pH 5.0) endosomal pH conditions. Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and the soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions.

Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

PubMed

Moayeri, Mahtab; Tremblay, Jacqueline M; Debatis, Michelle; Dmitriev, Igor P; Kashentseva, Elena A; Yeh, Anthony J; Cheung, Gordon Y C; Curiel, David T; Leppla, Stephen; Shoemaker, Charles B

2016-01-06

Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment

PubMed Central

Suo, Huayi; Zhao, Xin; Qian, Yu; Li, Guijie; Liu, Zhenhu; Xie, Jie; Li, Jian

2014-01-01

The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription–polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity. PMID:25464378

Short term effects of energy restriction and dietary fat sub-type on weight loss and disease risk factors.

PubMed

Tapsell, L; Batterham, M; Huang, X F; Tan, S-Y; Teuss, G; Charlton, K; Oshea, J; Warensjö, E

2010-06-01

Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. One-hundred and fifty overweight men and women were randomized into a 3month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with 10% polyunsaturated fatty acids (LF-PUFA); (3) low calorie (LF-LC) (-2MJ); (4) low calorie with 10% PUFA (LF-PUFA-LC). Primary outcomes were changes in body weight and body fat and secondary outcomes were changes in fasting levels of leptin, insulin, glucose, lipids and erythrocyte fatty acids. Changes in dietary intake were assessed using 3day food records. One-hundred and twenty-two participants entered the study and 95 completed the study. All groups lost weight and body fat (P<0.0001 time effect for both), but the LC groups lost more weight (P=0.026 for diet effect). All groups reduced total cholesterol levels (P<0.0001 time effect and P=0.017 intervention effect), but the LC and PUFA groups were better at reducing triacylglycerol levels (P=0.056 diet effect). HDL increased with LF-LC and LF-PUFA but not with LF-PUFA-LC (0.042 diet effect). The LF and LF-LC groups reported greater dietary fat reductions than the two PUFA groups (P=0.043). Energy restriction has the most potent effect on weight loss and lipids, but fat modification is also beneficial when energy restriction is more modest.

Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression

PubMed Central

Audette, Dylan S.; Anand, Deepti; So, Tammy; Rubenstein, Troy B.; Lachke, Salil A.; Lovicu, Frank J.; Duncan, Melinda K.

2016-01-01

Lens epithelial cells differentiate into lens fibers (LFs) in response to a fibroblast growth factor (FGF) gradient. This cell fate decision requires the transcription factor Prox1, which has been hypothesized to promote cell cycle exit in differentiating LF cells. However, we find that conditional deletion of Prox1 from mouse lenses results in a failure in LF differentiation despite maintenance of normal cell cycle exit. Instead, RNA-seq demonstrated that Prox1 functions as a global regulator of LF cell gene expression. Intriguingly, Prox1 also controls the expression of fibroblast growth factor receptors (FGFRs) and can bind to their promoters, correlating with decreased downstream signaling through MAPK and AKT in Prox1 mutant lenses. Further, culturing rat lens explants in FGF increased their expression of Prox1, and this was attenuated by the addition of inhibitors of MAPK. Together, these results describe a novel feedback loop required for lens differentiation and morphogenesis, whereby Prox1 and FGFR signaling interact to mediate LF differentiation in response to FGF. PMID:26657765

Prox1 and fibroblast growth factor receptors form a novel regulatory loop controlling lens fiber differentiation and gene expression.

PubMed

Audette, Dylan S; Anand, Deepti; So, Tammy; Rubenstein, Troy B; Lachke, Salil A; Lovicu, Frank J; Duncan, Melinda K

2016-01-15

Lens epithelial cells differentiate into lens fibers (LFs) in response to a fibroblast growth factor (FGF) gradient. This cell fate decision requires the transcription factor Prox1, which has been hypothesized to promote cell cycle exit in differentiating LF cells. However, we find that conditional deletion of Prox1 from mouse lenses results in a failure in LF differentiation despite maintenance of normal cell cycle exit. Instead, RNA-seq demonstrated that Prox1 functions as a global regulator of LF cell gene expression. Intriguingly, Prox1 also controls the expression of fibroblast growth factor receptors (FGFRs) and can bind to their promoters, correlating with decreased downstream signaling through MAPK and AKT in Prox1 mutant lenses. Further, culturing rat lens explants in FGF increased their expression of Prox1, and this was attenuated by the addition of inhibitors of MAPK. Together, these results describe a novel feedback loop required for lens differentiation and morphogenesis, whereby Prox1 and FGFR signaling interact to mediate LF differentiation in response to FGF. © 2016. Published by The Company of Biologists Ltd.

Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

PubMed

Hou, Jian-ming; Wu, Man; Lin, Qing-ming; Lin, Fan; Xue, Ying; Lan, Xu-hua; Chen, En-yu; Wang, Mei-li; Yang, Hai-yan; Wang, Feng-xiong

2014-08-01

The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 μg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 μg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 μM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

Enzyme That Makes You Cry-Crystal Structure of Lachrymatory Factor Synthase from Allium cepa.

PubMed

Silvaroli, Josie A; Pleshinger, Matthew J; Banerjee, Surajit; Kiser, Philip D; Golczak, Marcin

2017-09-15

The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFS in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of the START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.

Enzyme That Makes You Cry–Crystal Structure of Lachrymatory Factor Synthase from Allium cepa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silvaroli, Josie A.; Pleshinger, Matthew J.; Banerjee, Surajit

The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFSmore » in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of the START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.« less

Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.

PubMed

Oscherwitz, Jon; Yu, Fen; Jacobs, Jana L; Cease, Kemp B

2013-03-01

We previously showed that a multiple antigenic peptide (MAP) vaccine displaying amino acids (aa) 304 to 319 from the 2β2-2β3 loop of protective antigen was capable of protecting rabbits from an aerosolized spore challenge with Bacillus anthracis Ames strain. Antibodies to this sequence, referred to as the loop-neutralizing determinant (LND), are highly potent at neutralizing lethal toxin yet are virtually absent in rabbit and human protective antigen (PA) antiserum. While the MAP vaccine was protective against anthrax, it contains a single heterologous helper T cell epitope which may be suboptimal for stimulating an outbred human population. We therefore engineered a recombinant vaccine (Rec-LND) containing two tandemly repeated copies of the LND fused to maltose binding protein, with enhanced immunogenicity resulting from the p38/P4 helper T cell epitope from Schistosoma mansoni. Rec-LND was found to be highly immunogenic in four major histocompatibility complex (MHC)-diverse strains of mice. All (7/7) rabbits immunized with Rec-LND developed high-titer antibody, 6 out of 7 developed neutralizing antibody, and all rabbits were protected from an aerosolized spore challenge of 193 50% lethal doses (LD(50)) of the B. anthracis Ames strain. Survivor serum from Rec-LND-immunized rabbits revealed significantly increased neutralization titers and specific activity compared to prechallenge levels yet lacked PA or lethal factor (LF) antigenemia. Control rabbits immunized with PA, which were also completely protected, appeared sterilely immune, exhibiting significant declines in neutralization titer and specific activity compared to prechallenge levels. We conclude that Rec-LND may represent a prototype anthrax vaccine for use alone or potentially combined with PA-containing vaccines.

A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei

2013-01-01

Purpose: Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials. Methods and Materials: From 1990-2008, 442 patients with urothelial bladder carcinoma at University of Pennsylvania were prospectively followed aftermore » RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk. Results: On univariate analysis, pathologic stage {>=}pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage {>=}pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk ({<=}pT2), intermediate-risk ({>=}pT3 and {>=}10 nodes removed), and high-risk ({>=}pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01). Conclusions: This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.« less

Brain-Derived Neurotrophic Factor in Patients with Primary Open-Angle Glaucoma and Age-related Cataract.

PubMed

Shpak, Alexander A; Guekht, Alla B; Druzhkova, Tatiana A; Kozlova, Ksenia I; Gulyaeva, Natalia V

2018-02-01

To study brain-derived neurotrophic factor (BDNF) content in aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG). BDNF was studied in 57 patients with age-related cataract, 55 patients with POAG combined with cataract, and 29 healthy controls (one eye in each person). AH was sampled during cataract surgery. The levels of BDNF in LF and BS did not differ in cataract patients and controls. The concentration of BDNF (pg/mL) in patients with POAG and cataract was lower than in cataract patients in AH (35.2 ± 14.2 vs. 54.6 ± 29.6, P < 0.001), LF (78.0 ± 25.1 vs. 116.2 ± 43.1, P < 0.001), and BS (19230 ± 5960 vs. 22440 ± 7580, P < 0.02), while the AH/LF ratio was similar (0.46 ± 0.18 vs. 0.48 ± 0.19). The AH level of BDNF declined in early POAG and relatively increased in the next stages of the disease, inversely correlating with visual field index (Pearson's correlation coefficient r = -0.404, P = 0.002) and average retinal nerve fiber layer thickness (r = -0.322, P = 0.018). BDNF contents in LF and BS were also the lowest in early POAG. BDNF in AH strongly correlated with its content in LF (r = 0.66, P < 0.000). A formula was suggested to calculate the AH concentration of BDNF basing on its content in LF. BDNF contents are decreased in AH, LF, and BS of patients with POAG demonstrating a significant decrease in the early POAG and relative increase in the next stages of the disease. A strong correlation exists between BDNF contents in AH and LF.

Lactoferrin and oral diseases: current status and perspective in periodontitis

PubMed Central

Berlutti, Francesca; Pilloni, Andrea; Pietropaoli, Miriam; Polimeni, Antonella; Valenti, Piera

2012-01-01

Summary Lactoferrin (Lf), an iron-binding glycoprotein able to chelate two ferric ions per molecule, is a component of human secretions synthesized by exocrine glands and neutrophils in infection/inflammation sites. Lactoferrin in saliva represents an important defence factor against bacterial injuries including those related to Streptococcus mutans and periodontopathic bacteria through its ability to decrease bacterial growth, biofilm development, iron overload, reactive oxygen formation and inflammatory processes. A growing body of research suggests that inflammatory periodontal disease involves a failure of resolution pathways to restore tissue homeostasis. There is an important distinction between anti-inflammation and resolution; anti-inflammation is pharmacologic intervention in inflammatory pathways, whereas resolution involves biologic pathways restoring inflammatory homeostasis. An appropriate regulation of pro-inflammatory cytokine synthesis might be useful in reducing periodontal tissue destruction. Recently, the multi-functional IL-6 is emerging as an important factor able to modulate bone, iron and inflammatory homeostasis. Here, we report an overview of Lf functions as well as for the first time Lf anti-inflammatory ability against periodontitis in in vitro model and observational clinical study. In in vitro model, represented by gingival fibroblasts infected with Prevotella intermedia, Lf exerted a potent anti-inflammatory activity. In the observational clinical trial performed through bovine Lf (bLf) topically administered to volunteers suffering from periodontitis, bLf decreased cytokines, including IL-6 in crevicular fluid, edema, bleeding, pocket depth, gingival and plaque index, thus improving clinical attachment levels. Even if other clinical trials are required, these results provide strong evidence for a instead of an therapeutic potential of this multifunctional natural protein. PMID:22545184

Lactoferrin-derived peptides and Lactoferricin chimera inhibit virulence factor production and biofilm formation in Pseudomonas aeruginosa.

PubMed

Xu, G; Xiong, W; Hu, Q; Zuo, P; Shao, B; Lan, F; Lu, X; Xu, Y; Xiong, S

2010-10-01

To investigate the bactericidal activity of lactoferrin-derived peptides and a new LF-derived peptides chimera (LFchimera) against P. aeruginosa and the influence on virulence factors of P. aeruginosa. Lactoferricin (LFcin) and lactoferrampin (LFampin) are highly bioactive peptides isolated from the N-terminal region of lactoferrin (LF) by pepsin digestion. In this study, we designed LFchimera containing LFcin amino acids 17-30 and LFampin amino acids 268-284. Pseudomonas aeruginosa cells were incubated in medium with peptides at different concentrations, and then the assays of viability, pyocyanin, elastase activity and biofilm formation of P. aeruginosa were performed. We found that the concentration-dependent antibactericidal activity and down-regulating pyocyanin, elastase and biofilm formation of LFchimera were significantly stronger than those of LF, LFcin, LFampin or LFcin plus LFampin. Our results indicated that LF, LFcin, LFampin and LFchimera were potential candidates to combat P. aeruginosa, and LFchimera was the most effective in them. The new LFchimera has better activity against P. aeruginosa than LF, LFcin and LFampin and may be a promising new compound for treatment of P. aeruginosa infection. © 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.

Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.

PubMed

León-Sicairos, Nidia; Angulo-Zamudio, Uriel A; Vidal, Jorge E; López-Torres, Cynthia A; Bolscher, Jan G M; Nazmi, Kamran; Reyes-Cortes, Ruth; Reyes-López, Magda; de la Garza, Mireya; Canizalez-Román, Adrian

2014-10-01

Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million child deaths annually. Pneumococcus causes infections such as pneumonia, otitis media, meningitis, and sepsis. The human immune system includes antibacterial peptides and proteins such as lactoferrin (LF), but its activity against pneumococcus is not fully understood. The aim of this work was to evaluate the bactericidal effect of bovine lactoferrin (bLF) and the synthetic LF-peptides lactoferricin (LFcin17-30), lactoferrampin (LFampin265-284), and LFchimera against S. pneumoniae planktonic cells. The mechanism of damage was also investigated, as well as the impact of these peptides on the transcription levels of genes known to encode important virulence factors. S. pneumoniae planktonic cells were treated with bLF, LFcin17-30, LFampin265-284 and LFchimera at different time points. The viability of treated planktonic cells was assessed by dilution and plating (in CFU/ml). The interaction between LF and LF-peptides coupled to fluorescein was visualized using a confocal microscope and flow cytometry, whereas the damage at structural levels was observed by electron microscopy. Damage to bacterial membranes was further evaluated by membrane permeabilization by use of propidium iodide and flow cytometry, and finally, the expression of pneumococcal genes was evaluated by qRT-PCR. bLF and LFchimera were the best bactericidal agents. bLF and peptides interacted with bacteria causing changes in the shape and size of the cell and membrane permeabilization. Moreover, the luxS gene was down-regulated in bacteria treated with LF. In conclusion, LF and LFchimera have a bactericidal effect, and LF down-regulates genes involved in the pathogenicity of pneumococcus, thus demonstrating potential as new agents for the treatment of pneumococcal infections.

Detection of anthrax protective antigen (PA) using europium labeled anti-PA monoclonal antibody and time-resolved fluorescence ◊

PubMed Central

Stoddard, Robyn A.; Quinn, Conrad P.; Schiffer, Jarad M.; Boyer, Anne E.; Goldstein, Jason; Bagarozzi, Dennis A.; Soroka, Stephen D.; Dauphin, Leslie A.; Hoffmaster, Alex R.

2015-01-01

Inhalation anthrax is a rare but acute infectious disease following adsorption of Bacillus anthracis spores through the lungs. The disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. The early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time PCR. Consequently, there may be a significant delay in diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are therefore needed, particularly in the context of a large scale emergency response. The aim of this study was to evaluate the ability of monoclonal antibodies to detect anthrax toxin proteins that are secreted early in the course of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay. We selected monoclonal antibodies that could detect protective antigen (PA), as PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable detection limit (RDL) was 6.63 × 10−6 μM (0.551 ng/ml) for PA83 and 2.51 × 10−5 μM (1.58 ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA was detected in 9 out of 10 sera samples from anthrax confirmed case patients with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease. Anthrax Immune Globulin (AIG), which has been used in treatment of clinical anthrax, interfered with detection of PA. This study demonstrates a culture-independent method of diagnosing anthrax through use of monoclonal antibodies to detect PA and LF in the lethal toxin complex. PMID:24857756

Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax.

PubMed

Glinert, Itai; Bar-David, Elad; Sittner, Assa; Weiss, Shay; Schlomovitz, Josef; Ben-Shmuel, Amir; Mechaly, Adva; Altboum, Zeev; Kobiler, David; Levy, Haim

2016-08-01

Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (≥10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissue-inhibitor of metalloproteinases-1 over that of interleukin-1beta and metalloproteinases.

PubMed

Déage, V; Burger, D; Dayer, J M

1998-12-01

On direct cell-cell contact, stimulated T lymphocytes potently trigger the production of pro-inflammatory factors such as interleukin-1beta (IL-1beta) and matrix metalloproteinases (MMP-1 and MMP-9), as well as anti-inflammatory factors such as IL-1 receptor antagonist (IL-1Ra) and the tissue inhibitor of metalloproteinases (TIMP-1) in peripheral blood monocytes and the monocytic cell line THP-1. Such mechanisms might play an important part in many inflammatory diseases where tissue destruction occurs. To assess whether anti-inflammatory agents such as dexamethasone (DEX) and leflunomide (LF) would affect contact-activation of monocytic cells, T lymphocytes were stimulated by PMA and PHA in the presence or absence of increasing concentrations of drug. LF and DEX (10- 4 M) inhibited the ability of stimulated T lymphocytes to activate monocytic cells by 66-97% and 43-70%, respectively, depending on the readout product. Upon contact with T lymphocytes stimulated in the presence of 10- 5 M LF, the molar ratio of IL-1Ra/IL-1beta and TIMP-1/MMP-1 produced by THP-1 cells was enhanced 3.6- and 1.9-fold, respectively, whereas it was enhanced only 1.3- and 1.4-fold upon contact with T lymphocytes stimulated in the presence of 10- 4 M DEX. Therefore, LF tends to favor the inhibition of pro-inflammatory and matrix-destructive factors over that of anti-inflammatory factors and metalloproteinase inhibitors, thus interfering with both inflammation and tissue destruction. These experiments indicate that LF and DEX have the potential to affect the capacity of stimulated T lymphocytes to activate, on direct cell-cell contact, monocytic cells. Furthermore, flow cytometric analysis revealed that surface molecules of T lymphocytes that were partially involved in contact-signaling of monocytes (i.e., CD69 and CD11) were not modulated by either LF or DEX, suggesting that factors which remain to be identified were mainly involved in the activation of monocytes on direct cell-cell contact.

Community-based field implementation scenarios of a short message service reporting tool for lymphatic filariasis case estimates in Africa and Asia.

PubMed

Mableson, Hayley E; Martindale, Sarah; Stanton, Michelle C; Mackenzie, Charles; Kelly-Hope, Louise A

2017-01-01

Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted for global elimination by 2020. Currently there is considerable international effort to scale-up morbidity management activities in endemic countries, however there remains a need for rapid, cost-effective methods and adaptable tools for obtaining estimates of people presenting with clinical manifestations of LF, namely lymphoedema and hydrocele. The mHealth tool ' MeasureSMS-Morbidity ' allows health workers in endemic areas to use their own mobile phones to send clinical information in a simple format using short message service (SMS). The experience gained through programmatic use of the tool in five endemic countries across a diversity of settings in Africa and Asia is used here to present implementation scenarios that are suitable for adapting the tool for use in a range of different programmatic, endemic, demographic and health system settings. A checklist of five key factors and sub-questions was used to determine and define specific community-based field implementation scenarios for using the MeasureSMS-Morbidity tool in a range of settings. These factors included: (I) tool feasibility (acceptability; community access and ownership); (II) LF endemicity (high; low prevalence); (III) population demography (urban; rural); (IV) health system structure (human resources; community access); and (V) integration with other diseases (co-endemicity). Based on experiences in Bangladesh, Ethiopia, Malawi, Nepal and Tanzania, four implementation scenarios were identified as suitable for using the MeasureSMS-Morbidity tool for searching and reporting LF clinical case data across a range of programmatic, endemic, demographic and health system settings. These include: (I) urban, high endemic setting with two-tier reporting; (II) rural, high endemic setting with one-tier reporting; (III) rural, high endemic setting with two-tier reporting; and (IV) low-endemic, urban and rural setting with one-tier reporting. A decision-making framework built from the key factors and questions, and the resulting four implementation scenarios is proposed as a means of using the MeasureSMS-Morbidity tool. This framework will help national LF programmes consider appropriate methods to implement a survey using this tool to improve estimates of the clinical burden of LF. Obtaining LF case estimates is a vital step towards the elimination of LF as a public health problem in endemic countries.

Meal-induced thermogenesis and obesity: is a fat meal a risk factor for fat gain in children?

PubMed

Maffeis, C; Schutz, Y; Grezzani, A; Provera, S; Piacentini, G; Tatò, L

2001-01-01

Diet composition, in particular fat intake, has been suggested to be a risk factor for obesity in humans. Several mechanisms may contribute to explain the impact of fat intake on fat gain. One factor may be the low thermogenesis induced by a mixed meal rich in fat. In a group of 11 girls (10.1 +/- 0.3 yr), 6 obese (body mass index, 25.6 +/- 0.6 kg/m(2)), and 5 nonobese (body mass index, 19 +/- 1.6 kg/m(2)), we tested the hypothesis that a mixed meal rich in fat can elicit energy saving compared with an isocaloric and isoproteic meal rich in carbohydrate. The postabsorptive resting energy expenditure and the thermic effect of a meal (TEM) after a low fat (LF; 20% fat, 68% carbohydrate, and 12% protein) or an isocaloric (2500 kJ or 600 Cal) and isoproteic high fat (HF; 48% fat, 40% carbohydrate, and 12% protein) meal were measured by indirect calorimetry. Each girl repeated the test with a different, randomly assigned menu (HF or LF) 1 week after the first test. TEM, expressed as a percentage of energy intake was significantly higher after a LF meal than after a HF meal (6.5 +/- 0.7% vs. 4.3 +/- 0.4%; P < 0.01). The postprandial respiratory quotient (RQ) was significantly higher after a LF meal than after a HF meal (0.86 +/- 0.013 vs. 0.83 +/- 0.014; P < 0.001). The HF low carbohydrate meal induced a significantly lower increase in carbohydrate oxidation than the LF meal (20.3 +/- 6.2 vs. 61.3 +/- 7.8 mg/min; P < 0.001). On the contrary, fat oxidation was significantly higher after a HF meal than after a LF meal (-1.3 +/- 2.4 vs. -15.1 +/- 3.6 mg/min; P < 0.01). However, the postprandial fat storage was 8-fold higher after a HF meal than after a LF meal (17.2 +/- 1.7 vs. 1.9 +/- 1.8 g; P < 0.001). These results suggest that a high fat meal is able to induce lower thermogenesis and a higher positive fat balance than an isocaloric and isoproteic low fat meal. Therefore, diet composition per se must be taken into account among the various risk factors that induce obesity in children.

[Diabetes mellitus and nonalcoholic fatty liver disease: The verges of contingency].

PubMed

Bakulin, I G; Sandler, Yu G; Vinnitskaya, E V; Keiyan, V A; Rodionova, S V; Rotin, D L

To estimate the incidence of hepatic steatosis (HS) and liver fibrosis (LF) in patients with diabetes mellitus (DM), by applying the noninvasive techniques of liver fibroelastometry (LFE) and a battery of fibrotests (FTs); to determine their diagnostic value and to identify factors influencing the development of LF. A comprehensive examination was made in 82 diabetic patients (mean age, 56.7±12.7 years; p=0.033). The data were statistically evaluated using ROC curve analysis, correlation and single-factor analyses of variance, and multiple logistic regression analysis. FTs and LFE revealed that the DM patients had liver cirrhosis (LC) (METAVIR F4) in 12 (14.6%) and 15 (18.2%) patients, respectively. Those showed clinically significant fibrosis (METAVIR fibrosis stages F2-3) in 19 (23.1%) and 23 (28%) patients, respectively. Varying degrees of HS were present in 79 (96.3%) patients. LFE and FTs demonstrated comparable results in detecting LC (the area under the receiver operating characteristics curve (AUROC), 0.83 and 0.81, respectively). The development of LF is influenced by factors, such as the degree of HS, obesity, the activity of an inflammatory process, and the level of alanine aminotransferase and α2-macroglobulin. Diabetic patients are at high risk for NAFLD to develop LF and LC. LFE and FTs showed a comparably high accuracy in the diagnosis of LC in patients with DM and these may be used for screening. With allowance made for the existing risk factors of LF and LC, it is necessary to identify groups of patients with DM for further examination and follow-up. Patients who are diagnosed with stage F4 should be examined carefully to evaluate concurrent diseases and to make liver biopsy.

Microcystins Alter Chemotactic Behavior in Caenorhabditis elegans by Selectively Targeting the AWA Sensory Neuron

PubMed Central

Moore, Caroline E.; Lein, Pamela J.; Puschner, Birgit

2014-01-01

Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition. PMID:24918360

Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

PubMed Central

Roy, Kislay; Patel, Yogesh S; Kanwar, Rupinder K; Rajkhowa, Rangam; Wang, Xungai; Kanwar, Jagat R

2016-01-01

This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR−) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. PMID:26730188

Great Ears: Low-Frequency Sensitivity Correlates in Land and Marine Leviathans.

PubMed

Ketten, D R; Arruda, J; Cramer, S; Yamato, M

2016-01-01

Like elephants, baleen whales produce low-frequency (LF) and even infrasonic (IF) signals, suggesting they may be particularly susceptible to underwater anthropogenic sound impacts. Analyses of computerized tomography scans and histologies of the ears in five baleen whale and two elephant species revealed that LF thresholds correlate with basilar membrane thickness/width and cochlear radii ratios. These factors are consistent with high-mass, low-stiffness membranes and broad spiral curvatures, suggesting that Mysticeti and Proboscidea evolved common inner ear adaptations over similar time scales for processing IF/LF sounds despite operating in different media.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

PubMed

Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph

2017-03-10

To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

Ad libitum Mediterranean and Low Fat Diets both Significantly Reduce Hepatic Steatosis: a Randomized Controlled Trial.

PubMed

Properzi, Catherine; O'Sullivan, Therese A; Sherriff, Jill L; Ching, Helena L; Jeffrey, Garry P; Buckley, Rachel F; Tibballs, Jonathan; MacQuillan, Gerry C; Garas, George; Adams, Leon A

2018-05-05

Although diet induced weight loss is first-line treatment for patients with non-alcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for either improvement in NAFLD or associated cardio-metabolic risk factors regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets [Mediterranean (MD) or Low Fat (LF)] on hepatic steatosis and cardio-metabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs LF). Hepatic steatosis was determined via magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 subjects completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat but lower carbohydrate and sodium intakes compared to LF subjects (p<0.01). At week 12, hepatic steatosis had reduced significantly in both groups (p<0.01) and there was no difference in liver fat reduction between the groups (p=0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups [-1.6 (±2.1)kg in LF vs -2.1 (±2.5)kg in MD, (p=0.52)]. Within-group improvements in the Framingham risk score, total cholesterol, serum triglyceride, and HbA1c were observed in the MD (all p<0.05) but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%, p=0.048). Ad libitum low fat and Mediterranean diets both improve hepatic steatosis to a similar degree. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

High-Frequency Neuromuscular Electrical Stimulation Increases Anabolic Signaling.

PubMed

Mettler, Joni A; Magee, Dillon M; Doucet, Barbara M

2018-03-16

Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation settings to increase muscle mass and strength. However, the effects of NMES on muscle growth are not clear and no human studies have compared anabolic signaling between low-frequency (LF-) and high-frequency (HF-) NMES. The purpose of this study was to determine the skeletal muscle anabolic signaling response to an acute bout of LF- and HF-NMES. Eleven young healthy volunteers (6 men; 5 women) received an acute bout of LF- (20 Hz) and HF- (60 Hz) NMES. Muscle biopsies were obtained from the vastus lateralis muscle prior to the first NMES treatment and 30-mins following each NMES treatment. Phosphorylation of the following key anabolic signaling proteins was measured by Western blot and proteins are expressed as a ratio of phosphorylated to total: mammalian target of rapamycin (mTOR), p70-S6 kinase 1 (S6K1), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Compared to Pre-NMES, phosphorylation of mTOR was upregulated 40.2% for LF-NMES (P = 0.018) and 68.4% for HF-NMES (P < 0.0001) and HF-NMES was 29.3% greater than LF-NMES (P = 0.026). Phosphorylation of S6K1 after HF-NMES was 96.6% higher than Pre-NMES (P = 0.001), was not different between Pre-NMES and LF-NMES (although was 50.4% higher after LF-) or LF- and HF-NMES (P > 0.05). There were no differences between treatment conditions for 4E-BP1 phosphorylation (P > 0.05). An acute bout of LF- and HF-NMES upregulated anabolic signaling with HF-NMES producing a greater anabolic response compared to LF-NMES, suggesting that HF-stimulation may provide a stronger stimulus for processes that initiate muscle hypertrophy. Additionally, the stimulation frequency parameter should be considered by clinicians in the design of optimal NMES treatment protocols.

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, Abhinav V.; Pariser, Joseph J.; Pearce, Shane M.

2016-04-01

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined usingmore » follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.« less

Long-term effects of psychosocial factors of home and work on biomarkers of stress.

PubMed

Eller, Nanna Hurwitz; Kristiansen, Jesper; Hansen, Ase Marie

2011-02-01

The current study analyzed the relationship between psychosocial factors measured at baseline and heart rate variability (HRV) and salivary cortisol measured at baseline and again, six years later. In 2002 and 2008, measurements of HRV and salivary cortisol at three time points were obtained from 70 healthy participants (48 women and 22 men). The associations between the psychosocial factors measured in 2002 and the dependent variables, HRV and salivary cortisol measured in 2002 and 2008, were examined using a series of repeated measures ANCOVAs. The dependent variables were as follows: the logarithmically transformed levels of total power (LnTP), high frequency power (LnHF), the ratio between low and high frequency power (LnLF/HF) and salivary cortisol (LnCortisol). For women, high social status was associated with high LnTP, high LnHF, and low LnLF/HF. In work, lack of control was associated with low LnTP, and lack of support was associated with an increased LnLF/HF ratio. For men, high social status was associated with low LnTP, low LnHF and high LnCortisol. Greater number of hours spent doing housework was associated with both low LnLF/HF and low LnCortisol, whereas a large imbalance between effort and reward was associated with low LnTP and high LnCortisol. Despite the small sample size, this study demonstrated that psychosocial factors impact levels of activity in the allostatic systems. Copyright © 2010 Elsevier B.V. All rights reserved.

Antimicrobial peptide hLF1-11 directs granulocyte-macrophage colony-stimulating factor-driven monocyte differentiation toward macrophages with enhanced recognition and clearance of pathogens.

PubMed

van der Does, Anne M; Bogaards, Sylvia J P; Ravensbergen, Bep; Beekhuizen, Henry; van Dissel, Jaap T; Nibbering, Peter H

2010-02-01

The human lactoferrin-derived peptide hLF1-11 displays antimicrobial activities in vitro and is effective against infections with antibiotic-resistant bacteria and fluconazole-resistant Candida albicans in animals. However, the mechanisms underlying these activities remain largely unclear. Since hLF1-11 is ineffective in vitro at physiological salt concentrations, we suggested modulation of the immune system as an additional mechanism of action of the peptide. We investigated whether hLF1-11 affects human monocyte-macrophage differentiation and determined the antimicrobial activities of the resulting macrophages. Monocytes were cultured for 7 days with GM-CSF in the presence of hLF1-11, control peptide, or saline for various intervals. At day 6, the cells were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or heat-killed C. albicans for 24 h. Thereafter, the levels of cytokines in the culture supernatants, the expression of pathogen recognition receptors, and the antimicrobial activities of these macrophages were determined. The results showed that a short exposure of monocytes to hLF1-11 during GM-CSF-driven differentiation is sufficient to direct differentiation of monocytes toward a macrophage subset characterized by both pro- and anti-inflammatory cytokine production and increased responsiveness to microbial structures. Moreover, these macrophages are highly effective against C. albicans and Staphylococcus aureus. In conclusion, hLF1-11 directs GM-CSF-driven differentiation of monocytes toward macrophages with enhanced effector functions.

Discovery of a proteinaceous cellular receptor for a norovirus

PubMed Central

Orchard, Robert C.; Wilen, Craig B.; Doench, John G.; Baldridge, Megan T.; McCune, Broc T.; Lee, Ying-Chiang J.; Lee, Sanghyun; Pruett-Miller, Shondra M.; Nelson, Christopher A.; Fremont, Daved H.; Virgin, Herbert W.

2017-01-01

Human noroviruses (NoV) are a leading cause of gastroenteritis globally, yet host factors required for NoV infection are poorly understood. We identified host molecules essential for murine NoV (MNoV) induced cell death including CD300lf as a proteinaceous receptor. CD300lf is essential for MNoV binding and replication in cell lines and primary cells. Additionally, Cd300lf−/− mice are resistant to MNoV infection. Expression of CD300lf in human cells breaks the species barrier restricting MNoV replication. The crystal structure of the CD300lf ectodomain revealed a potential ligand binding cleft composed of residues critical for MNoV infection. Therefore, the presence of a proteinaceous receptor is the primary determinant of MNoV species tropism while other components of cellular machinery required for NoV replication are conserved between humans and mice. PMID:27540007

Collaborative study for establishment of the European Pharmacopoeia BRP batch 1 for diphtheria toxin.

PubMed

Sesardic, D; Prior, C; Daas, A; Buchheit, K H

2003-07-01

A stable liquid candidate Biological Reference Preparation (BRP) for diphtheria toxin was prepared in peptone buffer (nominal content of diphtheria toxin: 1 Lf/ml, 0.4 micro g/ml), filled in ampoules (filling volume: 1 ml) and characterised in a collaborative study. The toxin is to be used in the test "Absence of toxin and irreversibility of toxoid" as described in the current European Pharmacopoeia (Ph. Eur.) monograph Diphtheria Vaccine (Adsorbed) (2002:0443). Eleven laboratories assessed the specific activity of the preparation by in vivo and in vitro assays. The material is assumed to have satisfactory stability with a calculated predicted loss of activity of <1% per year at 4-8 degrees C. From the collaborative study, the specific activity was calculated as 77.6 (45-113) LD( 50)/ml (lethal challenge) and >75 000 Lr/Lf (intradermal challenge). The candidate BRP was successfully used in nine laboratories and confirmed suitable for use in the Vero cell test for "Absence of toxin and irreversibility of toxoid" as described in the Ph. Eur. monograph 2002:0443; i.e., concentrations of 5 x 10( -5) Lf/ml and below caused cytotoxic effects in the Vero cell test. Due to its liquid nature, the stability of the material will be monitored at regular intervals and preparation of a stable freeze-dried formulation will be considered for long-term use. Additional studies will be performed to confirm suitability of this BRP for other applications. The candidate BRP was adopted as the Ph. Eur. reference material for Diphtheria Toxin Batch 1 by the Ph. Eur. Commission at its session in March 2003.

Nitrogen losses and chemical parameters during co-composting of solid wastes and liquid pig manure.

PubMed

Vázquez, M A; de la Varga, D; Plana, R; Soto, M

2017-07-04

The aim of this research was to study nitrogen losses during the treatment of the liquid fraction (LF) of pig manure by co-composting and to establish the best conditions for compost production with higher nitrogen and low heavy metal contents. Windrows were constituted with the solid fraction (SF) of pig manure, different organic waste (SF of pig manure, sawdust and grape bagasse) as co-substrate and Populus spp. wood chips as bulking material and watered intensely with the LF. Results show that nitrogen losses ranged from 30% to 66% of initial nitrogen and were mainly governed by substrate to bulking mass ratio and liquid fraction to substrate (LF/S) ratio, and only secondarily by operational parameters. Nitrogen losses decreased from 55-65% at low LF/S ratios (1.7-1.9 m 3 /t total solids (TS)) to 30-39% at high LF/S ratios (4.4-4.7 m 3 /t TS). Therefore, integrating the LF in the composting process at high LF/S ratios favoured nitrogen recovery and conservation. Nitrogen in the fine fraction (ranging from 27% to 48% of initial nitrogen) was governed by operational parameters, namely pH and temperature. Final compost showed low content in most heavy metals, but Zn was higher than the limits for compost use in agriculture. Zn content in the obtained compost varied from 1863 to 3269 mg/kg dm, depending on several factors. The options for obtaining better quality composts from the LF of pig manure are selecting co-substrates with low heavy metal content and using them instead of the SF of pig manure.

Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction.

PubMed

Chen, Jun; Toyomasu, Yoshitaka; Hayashi, Yujiro; Linden, David R; Szurszewski, Joseph H; Nelson, Heidi; Farrugia, Gianrico; Kashyap, Purna C; Chia, Nicholas; Ordog, Tamas

2016-10-03

Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment. Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R 2 for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota. On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher abundance of Bacteroidetes and Proteobacteria and a lower abundance of Firmicutes than AL mice. Persistent growth failure can be induced by 97-day dietary restriction in young female mice and is associated with microbiota changes seen in lean mice and individuals and anorexia nervosa. IGF1 facilitates recovery of body weights and microbiota.

A novel live attenuated anthrax spore vaccine based on an acapsular Bacillus anthracis Sterne strain with mutations in the htrA, lef and cya genes.

PubMed

Chitlaru, Theodor; Israeli, Ma'ayan; Rotem, Shahar; Elia, Uri; Bar-Haim, Erez; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

2017-10-20

We recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htrA (High Temperature Requirement A) gene in the Bacillus anthracis Sterne veterinary vaccine strain. This vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental Sterne strain. Here, we report the evaluation of additional mutations in the lef and cya genes, encoding for the toxin components lethal factor (LF) and edema factor (EF), to further attenuate the SterneΔhtrA strain and improve its compatibility for human use. Accordingly, we constructed seven B. anthracis Sterne-derived strains exhibiting different combinations of mutations in the htrA, cya and lef genes. The various strains were indistinguishable in growth in vitro and in their ability to synthesise the protective antigen (PA, necessary for the elicitation of protection). In the sensitive murine model, we observed a gradual increase (ΔhtrA<ΔhtrAΔcya<ΔhtrAΔlef<ΔhtrAΔlefΔcya) in attenuation - up to 10 8 -fold relative to the parental Sterne vaccine strain. Most importantly, all various SterneΔhtrA derivative strains did not differ in their ability to elicit protective immunity in guinea pigs. Immunisation of guinea pigs with a single dose (10 9 spores) or double doses (>10 7 spores) of the most attenuated triple mutant strain SterneΔhtrAlef MUT Δcya induced a robust immune response, providing complete protection against a subsequent respiratory lethal challenge. Partial protection was observed in animals vaccinated with a double dose of as few as 10 5 spores. Furthermore, protective immune status was maintained in all vaccinated guinea pigs and rabbits for at least 40 and 30weeks, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

The brain adjusts grip forces differently according to gravity and inertia: a parabolic flight experiment

PubMed Central

White, Olivier

2015-01-01

In everyday life, one of the most frequent activities involves accelerating and decelerating an object held in precision grip. In many contexts, humans scale and synchronize their grip force (GF), normal to the finger/object contact, in anticipation of the expected tangential load force (LF), resulting from the combination of the gravitational and the inertial forces. In many contexts, GF and LF are linearly coupled. A few studies have examined how we adjust the parameters–gain and offset–of this linear relationship. However, the question remains open as to how the brain adjusts GF regardless of whether LF is generated by different combinations of weight and inertia. Here, we designed conditions to generate equivalent magnitudes of LF by independently varying mass and movement frequency. In a control experiment, we directly manipulated gravity in parabolic flights, while other factors remained constant. We show with a simple computational approach that, to adjust GF, the brain is sensitive to how LFs are produced at the fingertips. This provides clear evidence that the analysis of the origin of LF is performed centrally, and not only at the periphery. PMID:25717293

Production and characterization of tearless and non-pungent onion.

PubMed

Kato, Masahiro; Masamura, Noriya; Shono, Jinji; Okamoto, Daisaku; Abe, Tomoko; Imai, Shinsuke

2016-04-06

The onion lachrymatory factor (LF) is produced from trans-S-1-propenyl-L-cysteine sulfoxide (PRENCSO) through successive reactions catalyzed by alliinase (EC 4.4.1.4) and lachrymatory factor synthase (LFS), and is responsible for the tear inducing-property and the pungency of fresh onions. We developed tearless, non-pungent onions non-transgenically by irradiating seeds with neon-ion at 20 Gy. The bulbs obtained from the irradiated seeds and their offspring bulbs produced by selfing were screened by organoleptic assessment of tear-inducing property or HPLC analysis of LF production. After repeated screening and seed production by selfing, two tearless, non-pungent bulbs were identified in the third generation (M3) bulbs. Twenty M4 bulbs obtained from each of them showed no tear-inducing property or pungency when evaluated by 20 sensory panelists. The LF production levels in these bulbs were approximately 7.5-fold lower than those of the normal onion. The low LF production levels were due to reduction in alliinase activity, which was a result of low alliinase mRNA expression (less than 1% of that in the normal onion) and consequent low amounts of the alliinase protein. These tearless, non-pungent onions should be welcomed by all who tear while chopping onions and those who work in facilities where fresh onions are processed.

Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.

PubMed

Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

2017-03-20

Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

Effect of iron oxide loading on magnetoferritin structure in solution as revealed by SAXS and SANS.

PubMed

Melníková, L; Petrenko, V I; Avdeev, M V; Garamus, V M; Almásy, L; Ivankov, O I; Bulavin, L A; Mitróová, Z; Kopčanský, P

2014-11-01

Synthetic biological macromolecule of magnetoferritin containing an iron oxide core inside a protein shell (apoferritin) is prepared with different content of iron. Its structure in aqueous solution is analysed by small-angle synchrotron X-ray (SAXS) and neutron (SANS) scattering. The loading factor (LF) defined as the average number of iron atoms per protein is varied up to LF=800. With an increase of the LF, the scattering curves exhibit a relative increase in the total scattered intensity, a partial smearing and a shift of the match point in the SANS contrast variation data. The analysis shows an increase in the polydispersity of the proteins and a corresponding effective increase in the relative content of magnetic material against the protein moiety of the shell with the LF growth. At LFs above ∼150, the apoferritin shell undergoes structural changes, which is strongly indicative of the fact that the shell stability is affected by iron oxide presence. Copyright © 2014 Elsevier B.V. All rights reserved.

Identification, Characterization and Expression Profiling of Stress-Related Genes in Easter Lily (Lilium formolongi)

PubMed Central

Howlader, Jewel; Park, Jong-In; Robin, Arif Hasan Khan; Sumi, Kanij Rukshana; Nou, Ill-Sup

2017-01-01

Biotic and abiotic stresses are the major causes of crop loss in lily worldwide. In this study, we retrieved 12 defense-related expressed sequence tags (ESTs) from the NCBI database and cloned, characterized, and established seven of these genes as stress-induced genes in Lilium formolongi. Using rapid amplification of cDNA ends PCR (RACE-PCR), we successfully cloned seven full-length mRNA sequences from L. formolongi line Sinnapal lily. Based on the presence of highly conserved characteristic domains and phylogenetic analysis using reference protein sequences, we provided new nomenclature for the seven nucleotide and protein sequences and submitted them to GenBank. The real-time quantitative PCR (qPCR) relative expression analysis of these seven genes, including LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfUb, LfCyt-b5, and LfRab, demonstrated that they were differentially expressed in all organs examined, possibly indicating functional redundancy. We also investigated the qPCR relative expression levels under two biotic and four abiotic stress conditions. All seven genes were induced by Botrytis cinerea treatment, and all genes except LfHsp70-3 and LfHsp90 were induced by Botrytis elliptica treatment; these genes might be associated with disease tolerance mechanisms in L. formolongi. In addition, LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfUb, and LfCyt-b5 were induced by heat treatment, LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, and LfCyt-b5 were induced by cold treatment, and LfHsp70-1, LfHsp70-2, LfHsp70-3, LfHsp90, LfCy-b5, and LfRab were induced by drought and salt stress, indicating their likely association with tolerance to these stress conditions. The stress-induced candidate genes identified in this study provide a basis for further functional analysis and the development of stress-resistant L. formolongi cultivars.

Providing food to treat adolescents at risk for cardiovascular disease.

PubMed

de Ferranti, Sarah D; Milliren, Carly E; Denhoff, Erica Rose; Quinn, Nicolle; Osganian, Stavroula K; Feldman, Henry A; Ebbeling, Cara B; Ludwig, David S

2015-10-01

Diet modification is recommended to treat childhood cardiovascular (CV) risk factors; however, the optimal dietary strategy is unknown. In a randomized trial, the effect of a low-fat (LF) and a low-glycemic-load (LGL) reduced-calorie diet were examined in youth with overweight/obesity with CV risk factors. Using a novel intervention, we delivered LF or LGL meals and nutrition education to the home for 8 weeks (Intensive Phase), followed by 4 months Maintenance without food provision. Between-group differences in the change in insulin area under the curve (InsAUC) by oral glucose tolerance test and other risk factors were analyzed. Overall, participants (n = 27) showed substantial improvement during the Intensive Phase, including InsAUC (-59 ± 18.2 µU/ml × 120 min, P = 0.004), total cholesterol (-9.9 ± 3.6 mg/dl, P = 0.01), weight (-2.7 ± 0.5 kg, P < 0.001), waist circumference (-3.1 ± 0.8 cm, P < 0.001), HOMA-IR (-1.7 ± 0.4, P < 0.001), systolic blood pressure (-5 ± 1.4 mm Hg, P = 0.002), and CRP (-0.1 ± 0.1 mg/dl, P = 0.04). There were minimal between-group differences; the LF group showed greater declines in HDL (P = 0.005) and fasting glucose (P = 0.01) compared to the LGL group. Improvements waned during Maintenance. Home delivery of LF or LGL diets resulted in rapid and clinically important improvements in CV risk factors that diminished without food delivery and did not differ based on dietary intervention. If scalable, food provision may represent an alternative nutrition treatment strategy. © 2015 The Obesity Society.

Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet.

PubMed

Klempel, Monica C; Kroeger, Cynthia M; Varady, Krista A

2013-01-01

Alternate day fasting (ADF) with a low-fat (LF) diet is effective for weight loss and cardio-protection. However, the applicability of these findings is questionable as the majority of Americans consume a high-fat (HF) diet. The goal of this study was to determine if these beneficial changes in body weight and coronary heart disease (CHD) risk can be reproduced if an HF background diet is used in place of an LF diet during ADF. Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), which consisted of two phases: 1) a 2-week baseline weight maintenance period, and 2) an 8-week ADF weight loss period. All food was provided during the study. Body weight was reduced (P<0.0001) by ADF-HF (4.8%±1.1%) and by ADF-LF (4.2%±0.8%). Fat mass decreased (P<0.0001) by ADF-HF (5.4±1.5 kg) and ADF-LF (4.2±0.6 kg). Fat free mass remained unchanged. Waist circumference decreased (P<0.001) by ADF-HF (7.2±1.5 cm) and ADF-LF (7.3±0.9 cm). LDL cholesterol and triacylglycerol concentrations were reduced (P<0.001) by both interventions (ADF-HF: 18.3%±4.6%, 13.7%±4.8%; and ADF-LF: 24.8%±2.6%, 14.3%±4.4%). HDL cholesterol, blood pressure, and heart rate remained unchanged. There were no between-group differences for any parameter. These findings suggest that an ADF-HF diet is equally as effective as an ADF-LF diet in helping obese subjects lose weight and improve CHD risk factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

PubMed

Massie, Isobel; Dale, Sarah B; Daniels, Julie T

2015-06-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure

PubMed Central

Dale, Sarah B.; Daniels, Julie T.

2015-01-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE− RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP. PMID:25380529

Stereotactic radiosurgery for small brain metastases and implications regarding management with systemic therapy alone.

PubMed

Trifiletti, Daniel M; Hill, Colin; Cohen-Inbar, Or; Xu, Zhiyuan; Sheehan, Jason P

2017-09-01

While stereotactic radiosurgery (SRS) has been shown effective in the management of brain metastases, small brain metastases (≤10 mm) can pose unique challenges. Our aim was to investigate the efficacy of SRS in the treatment of small brain metastases, as well as elucidate clinically relevant factors impacting local failure (LF). We utilized a large, single-institution cohort to perform a retrospective analysis of patients with brain metastases up to 1 cm in maximal dimension. Clinical and radiosurgical parameters were investigated for an association with LF and compared using a competing risk model to calculate cumulative incidence functions, with death and whole brain radiotherapy serving as competing risks. 1596 small brain metastases treated with SRS among 424 patients were included. Among these tumors, 33 developed LF during the follow-up period (2.4% at 12 months following SRS). Competing risk analysis demonstrated that LF was dependent on tumor size (0.7% if ≤2 mm and 3.0% if 2-10 mm at 12 months, p = 0.016). Other factors associated with increasing risk of LF were the decreasing margin dose, increasing maximal tumor diameter, volume, and radioresistant tumors (each p < 0.01). 22 tumors (0.78%) developed radiographic radiation necrosis following SRS, and this incidence did not differ by tumor size (≤2 mm and 2-10 mm, p = 0.200). This large analysis confirms that SRS remains an effective modality in treatment of small brain metastases. In light of the excellent local control and relatively low risk of toxicity, patients with small brain metastases who otherwise have a reasonable expected survival should be considered for radiosurgical management.

Lung function, 25-hydroxyvitamin D concentrations and mortality in US adults

PubMed Central

Ford, ES

2015-01-01

OBJECTIVE To explore the associations between serum concentrations of vitamin D (25(OH)D) and all-cause mortality among US adults defined by lung function (LF) status, particularly among adults with obstructive LF (OLF). METHODS Data from 10 795 adults aged 20–79 years (685 with restrictive LF (RLF) and 1309 with OLF) who participated in the Third National Health and Nutrition Examination Survey (1988–1994), had a spirometric examination, and were followed through 2006 were included. RESULTS During 14.2 years of follow-up, 1792 participants died. Mean adjusted concentrations of 25(OH)D were 75.0 nmol/l (s.e. 0.7) for adults with normal LF (NLF), 70.4 nmol/l (s.e. 1.8) for adults with RLF, 75.5 nmol/l (s.e. 1.5) for adults with mild obstruction and 71.0 nmol/l (s.e. 1.9) among adults with moderate or worse obstruction (P = 0.030). After adjustment for sociodemographic factors, lifestyle factors, clinical variables and prevalent chronic conditions, a concentration of <25 nmol/l compared with ≥75 nmol//l was associated with mortality only among adults with NLF (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.03, 3.00). Among participants with OLF, adjusted HRs were 0.65 (95% CI 0.29, 1.48), 1.21 (95% CI 0.89, 1.66) and 0.97 (95% CI 0.78, 1.19) among those with concentrations <25, 25–<50 and 50–<75 nmol/l, respectively. CONCLUSIONS Baseline concentrations of 25(OH)D did not significantly predict mortality among US adults with impaired LF. PMID:25118000

WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals.

PubMed

Powell, Robin H; Behnke, Michael S

2017-05-15

Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance. © 2017. Published by The Company of Biologists Ltd.

CDKL5 regulates flagellar length and localizes to the base of the flagella in Chlamydomonas

PubMed Central

Tam, Lai-Wa; Ranum, Paul T.; Lefebvre, Paul A.

2013-01-01

The length of Chlamydomonas flagella is tightly regulated. Mutations in four genes—LF1, LF2, LF3, and LF4—cause cells to assemble flagella up to three times wild-type length. LF2 and LF4 encode protein kinases. Here we describe a new gene, LF5, in which null mutations cause cells to assemble flagella of excess length. The LF5 gene encodes a protein kinase very similar in sequence to the protein kinase CDKL5. In humans, mutations in this kinase cause a severe form of juvenile epilepsy. The LF5 protein localizes to a unique location: the proximal 1 μm of the flagella. The proximal localization of the LF5 protein is lost when genes that make up the proteins in the cytoplasmic length regulatory complex (LRC)—LF1, LF2, and LF3—are mutated. In these mutants LF5p becomes localized either at the distal tip of the flagella or along the flagellar length, indicating that length regulation involves, at least in part, control of LF5p localization by the LRC. PMID:23283985

Production and characterization of tearless and non-pungent onion

PubMed Central

Kato, Masahiro; Masamura, Noriya; Shono, Jinji; Okamoto, Daisaku; Abe, Tomoko; Imai, Shinsuke

2016-01-01

The onion lachrymatory factor (LF) is produced from trans-S-1-propenyl-L-cysteine sulfoxide (PRENCSO) through successive reactions catalyzed by alliinase (EC 4.4.1.4) and lachrymatory factor synthase (LFS), and is responsible for the tear inducing-property and the pungency of fresh onions. We developed tearless, non-pungent onions non-transgenically by irradiating seeds with neon-ion at 20 Gy. The bulbs obtained from the irradiated seeds and their offspring bulbs produced by selfing were screened by organoleptic assessment of tear-inducing property or HPLC analysis of LF production. After repeated screening and seed production by selfing, two tearless, non-pungent bulbs were identified in the third generation (M3) bulbs. Twenty M4 bulbs obtained from each of them showed no tear-inducing property or pungency when evaluated by 20 sensory panelists. The LF production levels in these bulbs were approximately 7.5-fold lower than those of the normal onion. The low LF production levels were due to reduction in alliinase activity, which was a result of low alliinase mRNA expression (less than 1% of that in the normal onion) and consequent low amounts of the alliinase protein. These tearless, non-pungent onions should be welcomed by all who tear while chopping onions and those who work in facilities where fresh onions are processed. PMID:27048847

Flexible Control of Safety Margins for Action Based on Environmental Variability.

PubMed

Hadjiosif, Alkis M; Smith, Maurice A

2015-06-17

To reduce the risk of slip, grip force (GF) control includes a safety margin above the force level ordinarily sufficient for the expected load force (LF) dynamics. The current view is that this safety margin is based on the expected LF dynamics, amounting to a static safety factor like that often used in engineering design. More efficient control could be achieved, however, if the motor system reduces the safety margin when LF variability is low and increases it when this variability is high. Here we show that this is indeed the case by demonstrating that the human motor system sizes the GF safety margin in proportion to an internal estimate of LF variability to maintain a fixed statistical confidence against slip. In contrast to current models of GF control that neglect the variability of LF dynamics, we demonstrate that GF is threefold more sensitive to the SD than the expected value of LF dynamics, in line with the maintenance of a 3-sigma confidence level. We then show that a computational model of GF control that includes a variability-driven safety margin predicts highly asymmetric GF adaptation between increases versus decreases in load. We find clear experimental evidence for this asymmetry and show that it explains previously reported differences in how rapidly GFs and manipulatory forces adapt. This model further predicts bizarre nonmonotonic shapes for GF learning curves, which are faithfully borne out in our experimental data. Our findings establish a new role for environmental variability in the control of action. Copyright © 2015 the authors 0270-6474/15/359106-16$15.00/0.

GALAXIES IN FILAMENTS HAVE MORE SATELLITES: THE INFLUENCE OF THE COSMIC WEB ON THE SATELLITE LUMINOSITY FUNCTION IN THE SDSS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Quan; Libeskind, N. I.; Tempel, E., E-mail: qguo@aip.de

We investigate whether the satellite luminosity function (LF) of primary galaxies identified in the Sloan Digital Sky Survey (SDSS) depends on whether the host galaxy is in a filament or not. Isolated primary galaxies are identified in the SDSS spectroscopic sample, and potential satellites (that are up to four magnitudes fainter than their hosts) are searched for in the much deeper photometric sample. Filaments are constructed from the galaxy distribution by the Bisous process. Isolated primary galaxies are divided into two subsamples: those in filaments and those not in filaments. We examine the stacked mean satellite LF of both themore » filament and nonfilament samples and find that, on average, the satellite LF of galaxies in filaments is significantly higher than those of galaxies not in filaments. The filamentary environment can increase the abundance of the brightest satellites (M {sub sat.} < M {sub prim.} + 2.0) by a factor of ∼2 compared with nonfilament isolated galaxies. This result is independent of the primary galaxy magnitude, although the satellite LF of galaxies in the faintest magnitude bin is too noisy to determine if such a dependence exists. Because our filaments are extracted from a spectroscopic flux-limited sample, we consider the possibility that the difference in satellite LF is due to a redshift, color, or environmental bias, finding these to be insufficient to explain our result. The dependence of the satellite LF on the cosmic web suggests that the filamentary environment may have a strong effect on the efficiency of galaxy formation.« less

Galaxies in Filaments have More Satellites: The Influence of the Cosmic Web on the Satellite Luminosity Function in the SDSS

NASA Astrophysics Data System (ADS)

Guo, Quan; Tempel, E.; Libeskind, N. I.

2015-02-01

We investigate whether the satellite luminosity function (LF) of primary galaxies identified in the Sloan Digital Sky Survey (SDSS) depends on whether the host galaxy is in a filament or not. Isolated primary galaxies are identified in the SDSS spectroscopic sample, and potential satellites (that are up to four magnitudes fainter than their hosts) are searched for in the much deeper photometric sample. Filaments are constructed from the galaxy distribution by the Bisous process. Isolated primary galaxies are divided into two subsamples: those in filaments and those not in filaments. We examine the stacked mean satellite LF of both the filament and nonfilament samples and find that, on average, the satellite LF of galaxies in filaments is significantly higher than those of galaxies not in filaments. The filamentary environment can increase the abundance of the brightest satellites (M sat. < M prim. + 2.0) by a factor of ~2 compared with nonfilament isolated galaxies. This result is independent of the primary galaxy magnitude, although the satellite LF of galaxies in the faintest magnitude bin is too noisy to determine if such a dependence exists. Because our filaments are extracted from a spectroscopic flux-limited sample, we consider the possibility that the difference in satellite LF is due to a redshift, color, or environmental bias, finding these to be insufficient to explain our result. The dependence of the satellite LF on the cosmic web suggests that the filamentary environment may have a strong effect on the efficiency of galaxy formation.

Ova fecundity in Scottish Atlantic salmon Salmo salar: predictions, selective forces and causal mechanisms.

PubMed

Bacon, P J; MacLean, J C; Malcolm, I A; Gurney, W S C

2012-08-01

Ova fecundities of Scottish Atlantic salmon Salmo salar, predicted from log(10) regression of ova numbers and female fork length (L(F)), differed widely between upland and lowland stocks within the same river, whereas sea-age, river and year factors had insignificant effects on fecundity once L(F) was accounted for. For upland fish, the relationship between log(10)L(F) and log(10) ova mass (M(O)) was stable between two datasets collected 40 years apart. Although upland and lowland females both produced comparable log(10)M(O) (log(10)L(F))(-1), lowland females partitioned this into 45% more, but smaller ova, whereas upland females produced fewer, but larger, eggs. The possible causes and implications of this are discussed for evolutionary perspectives (lifetime production), population structure (local tributary v. large catchments; environmental effects), population dynamics and stability (density-dependent control mechanisms) and fisheries management (stock-recruitment; short and long-term stock sustainability). © 2012 Marine Scotland. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Local control of brain metastases after stereotactic radiosurgery: the impact of whole brain radiotherapy and treatment paradigm

PubMed Central

Black, Paul J.; Page, Brandi R.; Lucas, John T.; Qasem, Shadi A.; Watabe, Kounosuke; Ruiz, Jimmy; Laxton, Adrian W.; Tatter, Stephen B.; Debinski, Waldemar; Chan, Michael D.

2016-01-01

Purpose We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). Methods and materials Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. Results Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). Conclusions WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS. PMID:29296433

Reduced heart rate variability and vagal tone in anxiety: trait versus state, and the effects of autogenic training.

PubMed

Miu, Andrei C; Heilman, Renata M; Miclea, Mircea

2009-01-28

This study investigated heart rate variability (HRV) in healthy volunteers that were selected for extreme scores of trait anxiety (TA), during two opposite psychophysiological conditions of mental stress, and relaxation induced by autogenic training. R-R intervals, HF and LF powers, and LF/HF ratios were derived from short-term electrocardiographic recordings made during mental stress and relaxation by autogenic training, with respiratory rate and skin conductance being controlled for in all the analyses. The main finding was that high TA was associated with reduced R-R intervals and HF power across conditions. In comparison to mental stress, autogenic training increased HRV and facilitated the vagal control of the heart. There were no significant effects of TA or the psychophysiological conditions on LF power, or LF/HF ratio. These results support the view that TA, which is an important risk factor for anxiety disorders and predictor of cardiovascular morbidity and mortality, is associated with autonomic dysfunction that seems likely to play a pathogenetic role in the long term.

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

PubMed

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Inhibitory effects of bovine lactoferrin and lactoferricin B on Enterobacter sakazakii.

PubMed

Wakabayashi, Hiroyuki; Yamauchi, Koji; Takase, Mitsunori

2008-03-01

The susceptibility of Enterobacter sakazakii, a food-borne pathogen, to several metal-bound forms of bovine lactoferrin (LF), pepsin-hydrolyzed LF (LF-hyd), and LF-derived peptide lactoferricin B (LFcin B) was tested. MIC and MBC testing revealed that 4 strains of E. sakazakii show susceptibility to apo- and Cu-LF, LF-hyd, and LFcin B, but not to Fe-LF, similarly to Escherichia coli. A growth curve test indicated that E. sakazakii was inhibited in a dose-dependent manner by apo-LF at 0.5 to 8 mg/ml. Even after being heated at 80 degrees C, LF at above 1 mg/ml inhibited the bacterial growth. These results suggest that bovine LF-related compounds may be useful for the inhibition of E. sakazakii in foods.

Kinetic and thermodynamic parameters for heat denaturation of human recombinant lactoferrin from rice.

PubMed

Castillo, Eduardo; Pérez, María Dolores; Franco, Indira; Calvo, Miguel; Sánchez, Lourdes

2012-06-01

Heat denaturation of recombinant human lactoferrin (rhLf) from rice with 3 different iron-saturation degrees, holo rhLf (iron-saturated), AsIs rhLf (60% iron saturation), and apo rhLf (iron-depleted), was studied. The 3 forms of rhLf were subjected to heat treatment, and the kinetic and thermodynamic parameters of the denaturation process were determined. Thermal denaturation of rhLf was assessed by measuring the loss of reactivity against specific antibodies. D(t) values (time to reduce 90% of immunoreactivity) decreased with increasing temperature of treatment for apo and holo rhLf, those values being higher for the iron-saturated form, which indicates that iron confers thermal stability to rhLf. However, AsIs rhLf showed a different behaviour with an increase in resistance to heat between 79 °C and 84 °C, so that the kinetic parameters could not be calculated. The heat denaturation process for apo and holo rhLf was best described assuming a reaction order of 1.5. The activation energy of the denaturation process was 648.20 kJ/mol for holo rhLf and 406.94 kJ/mol for apo rhLf, confirming that iron-depleted rhLf is more sensitive to heat treatment than iron-saturated rhLf.

Comparison of the effect of daily consumption of probiotic compared with low-fat conventional yogurt on weight loss in healthy obese women following an energy-restricted diet: a randomized controlled trial.

PubMed

Madjd, Ameneh; Taylor, Moira A; Mousavi, Neda; Delavari, Alireza; Malekzadeh, Reza; Macdonald, Ian A; Farshchi, Hamid R

2016-02-01

Despite evidence for the beneficial effects of probiotics and low-fat dairy products, to our knowledge, no study has compared the beneficial effect on weight loss of consuming a probiotic yogurt (PY) compared with a standard low-fat yogurt (LF) during a hypoenergetic program. We compared the effect of the PY with LF yogurt consumption on body weight and cardiometabolic risk factors in women during a weight-loss program. Overweight and obese women [body mass index (in kg/m(2)): 27-40; age: 18-50 y) who usually consumed standard LFs were asked to consume either PY or LF every day with their main meals for 12 wk while following a weight-loss program. A total of 89 participants were randomly assigned to one of the 2 intervention groups. Baseline variables were not significantly different between groups. A statistically significant reduction in anthropometric measurements and significant improvements in cardiometabolic risk characteristics were observed over the 12 wk in both groups. However, no significant differences in weight loss and anthropometric measurements were seen between groups after the intervention. Compared with the LF group, the PY group had a greater (mean ± SD) decrease in total cholesterol (PY = -0.36 ± 0.10 mmol/L, LF = -0.31 ± 0.10 mmol/L; P = 0.024), low-density lipoprotein cholesterol (PY = -0.35 ± 0.10 mmol/L, LF = -0.31 ± 0.11 mmol/L; P = 0.018), homeostasis model assessment of insulin resistance (PY = -0.55 ± 0.32, LF = -0.42 ± 0.20; P = 0.002), 2-h postprandial glucose (PY = -0.61 ± 0.24 mmol/L, LF = -0.44 ± 0.19 mmol/L; P < 0.001), and fasting insulin concentration (PY = -1.76 ± 1.01 mU/mL, LF = -1.32 ± 0.62 mU/mL; P = 0.002), as secondary endpoints after the study. No significant differences were found for fasting plasma glucose, high-density lipoprotein cholesterol, or triglycerides within both groups after the 12 wk. Consumption of PY compared with LF with main meals showed no significant effects on weight loss. However, it may have positive effects on lipid profiles and insulin sensitivity during a weight-loss program. This trial was registered at http://www.irct.ir/ as IRCT201402177754N8. © 2016 American Society for Nutrition.

Effect of iron saturation level of lactoferrin on osteogenic activity in vitro and in vivo.

PubMed

Wang, X Y; Guo, H Y; Zhang, W; Wen, P C; Zhang, H; Guo, Z R; Ren, F Z

2013-01-01

We studied the effect of iron saturation level on the osteogenic activity of lactoferrin (LF) in vitro and in vivo. Different iron saturation levels of LF (1.0, 9.0, 38, 58, and 96%) were prepared as the following samples: apo-LF, LF-9, LF-38, LF-58, and holo-LF. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we observed that the stimulating osteoblast proliferation activity of LF in vitro decreased with increasing iron saturation level at 100 and 1,000 μg/mL. In vivo, 4-wk-old ICR Swiss male mice were randomly divided into 4 groups: blank control (physiological saline), negative control (BSA), apo-LF, and holo-LF. Four groups of mice were injected subcutaneously with physiological saline, BSA, apo-LF, or holo-LF over the calvarial surface twice a day for 5 consecutive days at a dose of 4 mg/kg per day. Bone histomorphometry showed that new bone formation (assessed using tetracycline-HCl labels) tended to be stronger with apo-LF than with holo-LF. Using fluorescence spectroscopy and circular dichroism measurements, we found that exposure of tryptophan increased, α-helix content increased, but β-structure content decreased with increasing iron saturation level. These findings indicated that the osteogenic activity of LF decreases with increasing iron saturation level in vitro and in vivo, which may be related to conformational changes in LF. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Urban lymphatic filariasis in the metropolis of Dar es Salaam, Tanzania

PubMed Central

2013-01-01

Background The last decades have seen a considerable increase in urbanization in Sub-Saharan Africa, and it is estimated that over 50% of the population will live in urban areas by 2040. Rapid growth of cities combined with limited economic resources often result in informal settlements and slums with favorable conditions for proliferation of vectors of lymphatic filariasis (LF). In Dar es Salaam, which has grown more than 30 times in population during the past 55 years (4.4 million inhabitants in 2012), previous surveys have indicated high prevalences of LF. This study investigated epidemiological aspects of LF in Dar es Salaam, as a background for planning and implementation of control. Methods Six sites with varying distance from the city center (3–30 km) and covering different population densities, socioeconomic characteristics, and water, sewerage and sanitary facilities were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigen (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Structured questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Results The study indicated that a tremendous decrease in the burden of LF infection had occurred, despite haphazard urbanisation. Contributing factors may be urban malaria control targeting Anopheles vectors, short survival time of the numerous Culex quinquefasciatus vectors in the urban environment, widespread use of bed nets and other mosquito proofing measures, and mass drug administration (MDA) in 2006 and 2007. Although the level of ongoing transmission was low, the burden of chronic LF disease was still high. Conclusions The development has so far been promising, but continued efforts are necessary to ensure elimination of LF as a public health problem. These will include improving the awareness of people about the role of mosquitoes in transmission of LF, more thorough implementation of environmental sanitation to reduce Cx. quinquefasciatus breeding, continued MDA to high-risk areas, and set-up of programmes for management of chronic LF disease. PMID:24289718

Nuclear and cytoplasmic delivery of lactoferrin in glioma using chitosan nanoparticles: Cellular location dependent-action of lactoferrin.

PubMed

Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

2018-08-01

Lactoferrin (Lf) exerts anti-cancer effects on glioma, however, the exact mechanism remains unclear. Despite possessing a nuclear localization sequence (NLS), Lf was found to allocate only in the cytoplasm of glioma 261. Lf was therefore loaded into nuclear and cytoplasmic targeted nanoparticles (NPs) to determine whether nuclear delivery of Lf would enhance its anti-cancer effect. Upon treatment with 300 and 800 µg/mL Lf loaded chitosan NPs, nuclear targeted Lf-NPs showed 1.3 and 2.7 folds increase in cell viability, whereas cytoplasmic targeted Lf-NPs at 300 µg/mL decreased cell viability by 0.8 folds in comparison to free Lf and controls. Results suggest that the cytotoxicity of Lf on glioma is attributable to its cytoplasmic allocation. Nuclear delivery of Lf induced cell proliferation rather than cytotoxicity, indicating that the mode of action of Lf in glioma is cell location dependent. This calls for caution about the general use of Lf as an anti-cancer protein. Copyright © 2018. Published by Elsevier B.V.

Selected Topics in Light Front Field Theory and Applications to the High Energy Phenomena

NASA Astrophysics Data System (ADS)

Kundu, Rajen

1999-10-01

In this thesis, we have presented some of the aspects of light-front (LF) field theory through their successful application in the Deep Inelastic Scattering (DIS). We have developed a LFQCD Hamiltonian description of the DIS structure functions starting from Bjorken-Johnson-Low limit of virtual forward Compton scattering amplitude and using LF current commutators. We worked in the LF gauge A^+=0 and used the old-fashioned LFQCD perturbation theory in our calculations. The importance of our work are summarized below. Our approach shares the intution of parton model and addresses directly the structure functions, which are experimental objects, instead of its moments as in OPE method. Moreover, it can potentially incorporate the non-perturbative contents of the structure functions as we have demonstrated by introducing a new factorization scheme. In the context of nucleonic helicity structure, the well known gauge fixed LF helicity operator is shown to provide consistent physical information and helps us defining new relevant structure functions. The anomalous dimensions relevant for the Q^2-evolution of such structure functions are calculated. Our study is important in establishing the equivalance of LF field theory and the usual equal-time one through perturbative calculations of the dressed parton structure functions reproducing the well known results. Also the importance of Gallilean boost symmetry in understanding the correctness of any higher order calculation using (x^+)-ordered LFQCD perturbation theory are emphasized.

Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space.

PubMed

Daithankar, Vidyadhar N; Farrell, Scott R; Thorpe, Colin

2009-06-09

Augmenter of liver regeneration (ALR) is both a growth factor and a sulfhydryl oxidase that binds FAD in an unusual helix-rich domain containing a redox-active CxxC disulfide proximal to the flavin ring. In addition to the cytokine form of ALR (sfALR) that circulates in serum, a longer form, lfALR, is believed to participate in oxidative trapping of reduced proteins entering the mitochondrial intermembrane space (IMS). This longer form has an 80-residue N-terminal extension containing an additional, distal, CxxC motif. This work presents the first enzymological characterization of human lfALR. The N-terminal region conveys no catalytic advantage toward the oxidation of the model substrate dithiothreitol (DTT). In addition, a C71A or C74A mutation of the distal disulfide does not increase the turnover number toward DTT. Unlike Erv1p, the yeast homologue of lfALR, static spectrophotometric experiments with the human oxidase provide no evidence of communication between distal and proximal disulfides. An N-terminal His-tagged version of human Mia40, a resident oxidoreductase of the IMS and a putative physiological reductant of lfALR, was subcloned and expressed in Escherichia coli BL21 DE3 cells. Mia40, as isolated, shows a visible spectrum characteristic of an Fe-S center and contains 0.56 +/- 0.02 atom of iron per subunit. Treatment of Mia40 with guanidine hydrochloride and triscarboxyethylphosphine hydrochloride during purification removed this chromophore. The resulting protein, with a reduced CxC motif, was a good substrate of lfALR. However, neither sfALR nor lfALR mutants lacking the distal disulfide could oxidize reduced Mia40 efficiently. Thus, catalysis involves a flow of reducing equivalents from the reduced CxC motif of Mia40 to distal and then proximal CxxC motifs of lfALR to the flavin ring and, finally, to cytochrome c or molecular oxygen.

Augmenter of Liver Regeneration: Substrate Specificity of a Flavin-dependent Oxidoreductase from the Mitochondrial Intermembrane Space†

PubMed Central

Daithankar, Vidyadhar N.; Farrell, Scott R.; Thorpe, Colin

2009-01-01

Augmenter of liver regeneration (ALR) is both a growth factor and a sulfhydryl oxidase that binds FAD in an unusual helix-rich domain containing a redox-active CxxC disulfide proximal to the flavin ring. In addition to the cytokine form of ALR (sfALR) that circulates in serum, a longer form, lfALR, is believed to participate in oxidative trapping of reduced proteins entering the mitochondrial intermembrane space (IMS). This longer form has an 80-residue N-terminal extension containing an additional, distal, CxxC motif. This work presents the first enzymological characterization of human lfALR. The N-terminal region conveys no catalytic advantage towards the oxidation of the model substrate dithiothreitol (DTT). In addition, C71A or C74A mutations of the distal disulfide do not increase the turnover number towards DTT. Unlike Erv1p, the yeast homolog of lfALR, static spectrophotometric experiments of the human oxidase provide no evidence for communication between distal and proximal disulfides. An N-terminal his-tagged version of human Mia40, a resident oxidoreductase of the IMS and a putative physiological reductant of lfALR, was subcloned and expressed in Escherichia coli BL21 DE3 cells. Mia40, as isolated, shows a visible spectrum characteristic of an Fe/S center and contains 0.56 ± 0.02 atoms of iron per subunit. Treatment of Mia40 with guanidine hydrochloride and triscarboxyethylphosphine hydrochloride during purification removed this chromophore. The resulting protein, with a reduced CxC motif, was a good substrate of lfALR. However, neither sfALR, nor lfALR mutants lacking the distal disulfide, could oxidize reduced Mia40 efficiently. Thus, catalysis involves a flow of reducing equivalents from the reduced CxC motif of Mia40, to distal- and then proximal CxxC motifs of lfALR, to the flavin ring, and, finally, to cytochrome c or molecular oxygen. PMID:19397338

A geometrical shift results in erroneous appearance of low frequency tissue eddy current induced phase maps.

PubMed

Mandija, Stefano; van Lier, Astrid L H M W; Katscher, Ulrich; Petrov, Petar I; Neggers, Sebastian F W; Luijten, Peter R; van den Berg, Cornelis A T

2016-09-01

Knowledge on low frequency (LF) tissue conductivity is relevant for various biomedical purposes. To obtain this information, LF phase maps arising from time-varying imaging gradients have been demonstrated to create a LF conductivity contrast. Essential in this methodology is the subtraction of phase images acquired with opposite gradient polarities to separate LF and RF phase effects. Here we demonstrate how sensitive these subtractions are with respect to geometrical distortions. The effect of geometrical distortions on LF phase maps is mathematically defined. After quantifying typical geometrical distortions, their effects on LF phase maps are evaluated using conductive phantoms. For validation, electromagnetic simulations of LF phase maps were performed. Even sub-voxel distortions of 10% of the voxel size, measured for a typical LF MR sequence, cause leakage of RF phase into LF phase of several milli-radians, leading to a misleading pattern of LF phase maps. This leakage is mathematically confirmed, while simulations indicate that the expected LF phase should be in order of micro-radians. The conductivity scaling of LF phase maps is attributable to the RF phase leakage, thus dependent on the RF conductivity. In fact, simulations show that the LF phase is not measurable. Magn Reson Med 76:905-912, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Antimicrobial potential for the combination of bovine lactoferrin or its hydrolysate with lactoferrin-resistant probiotics against foodborne pathogens.

PubMed

Chen, P-W; Jheng, T T; Shyu, C-L; Mao, F C

2013-03-01

Previous reports have shown that several probiotic strains can resist the antibacterial activity of bovine lactoferrin (bLf), but the results are inconsistent. Moreover, a portion of orally administered apo-bLf is digested in vivo by pepsin to yield bLf hydrolysate, which produces stronger antibacterial activity than that observed with apo-bLf. However, whether bLf hydrolysate affects the growth of probiotic strains is unclear. Therefore, various probiotic strains in Taiwan were collected and evaluated for activity against apo-bLf and bLf hydrolysate in vitro. Thirteen probiotic strains were evaluated, and the growth of Lactobacillus acidophilus ATCC 4356, Lactobacillus salivarius ATCC 11741, Lactobacillus rhamnosus ATCC 53103, Bifidobacterium longum ATCC 15707, and Bifidobacterium lactis BCRC 17394 were inhibited by both apo-bLf and bLf hydrolysate. The growth of 8 strains were not affected by apo-bLf and bLf hydrolysate, including L. rhamnosus ATCC 7469, Lactobacillus reuteri ATCC 23272, Lactobacillus fermentum ATCC 11739, Lactobacillus coryniformis ATCC 25602, L. acidophilus BCRC 14065, Bifidobacterium infantis ATCC 15697, Bifidobacterium bifidum ATCC 29521, and Pediococcus acidilactici ATCC 8081. However, apo-bLf and its hydrolysate inhibited the growth of foodborne pathogens, including Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the supernatants produced by L. fermentum, B. lactis, and B. longum inhibited the growth of most pathogens. Importantly, a combination of apo-bLf or bLf hydrolysate with the supernatants of cultures of the organisms described above showed synergistic or partially synergistic effects against the growth of most of the selected pathogens. In conclusion, several probiotic strains are resistant to apo-bLf and bLf hydrolysate, warranting clinical studies to evaluate the antimicrobial potential for the combination of apo-bLf or its hydrolysate with specific probiotics. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hydroxyapatite nanorod and microsphere functionalized with bioactive lactoferrin as a new biomaterial for enhancement bone regeneration.

PubMed

Shi, Pujie; Wang, Qun; Yu, Cuiping; Fan, Fengjiao; Liu, Meng; Tu, Maolin; Lu, Weihong; Du, Ming

2017-07-01

Lactoferrin (LF) has been recently recognized as a promising new novel bone growth factor for the beneficial effects on bone cells and promotion of bone growth. Currently, it has been attracted wide attention in bone regeneration as functional food additives or a potential bioactive protein in bone tissue engineering. The present study investigated the possibility that hydroxyapatite (HAP) particles, a widely used bone substitute material for high biocompatibility and osteoconductivity, functionalized with lactoferrin as a composite material are applied to bone tissue engineering. Two kinds of hydroxyapatite samples with different sizes, including nanorods and microspheres particles, were functionalized with lactoferrin molecules, respectively. A detailed characterization of as-prepared HAP-LF complex is presented, combining thermal gravimetric analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). Zeta potential and the analysis of electrostatic surface potential of lactoferrin were carried to reveal the mechanism of adsorption. The effects of HAP-LF complex on MC3T3-E1 osteoblast proliferation and morphology were systematically evaluated at different culture time. Interestingly, results showed that cell viability of HAP-LF group was significantly higher than HAP group indicating that the HAP-LF can improve the biocompatibility of HAP, which mainly originated from a combination of HAP-LF interaction. These results indicated that hydroxyapatite particles can work as a controlled releasing carrier of lactoferrin successfully, and lactoferrin showed better potentiality on using in the field of bone regeneration by coupling with hydroxyapatite. This study would provide a new biomaterial and might offer a new insight for enhancement of bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Antibacterial activity of recombinant human lactoferrin from rice: effect of heat treatment.

PubMed

Conesa, Celia; Rota, Carmen; Castillo, Eduardo; Pérez, María-Dolores; Calvo, Miguel; Sánchez, Lourdes

2009-06-01

The antibacterial activity of recombinant human lactoferrin from rice (rhLF) compared with that of human milk lactoferrin (hLF) was evaluated against Escherichia coli O157:H7, Salmonella Enteritidis and Listeria monocytogenes. The hydrolysates of rhLF and hLF were found to be more active than native proteins against E. coli O157:H7, and their activity was independent of their iron saturation. The effect of different heat treatments on the antibacterial activity of apo-rhLF was studied and compared with hLF. We observed that an HTST pasteurization treatment did not affect the antimicrobial activity of lactoferrin against the pathogens studied. Furthermore, the activity of apo-rhLF and hLF against E. coli O157:H7 and L. monocytogenes in UHT milk and whey was assayed, finding a decrease in the number of bacteria, although lower than that observed in a broth medium. This study shows the similar antibacterial activity of rhLF and hLF which is important in order to consider the addition of rhLF as a supplement in special products.

Measurement of the magneto-optical correlation length in turbid media

NASA Astrophysics Data System (ADS)

Lenke, Ralf; Eisenmann, Christoph; Reinke, Daniel; Maret, Georg

2002-11-01

In multiple light scattering media, magnetic field induced circular birefringence (Faraday effect) influences interference effects such as speckle pattern or coherent backscattering. It was predicted that in the diffusive regime the relevant correlation length with respect to the Faraday rotation l*F differs, in general, from the transport mean free path l*. We have experimentally verified the prediction that the ratio l*F/l* equals 2 for Rayleigh scattering and decreases to 1 with increasing scatterer size. We also discuss the influence of the structure factor on l*F.

Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Binkley, Michael S.; Trakul, Nicholas; Jacobs, Lisa Rose

Purpose: Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes. Methods and Materials: We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses. Results: We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-upmore » was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED{sub 10}) of <100 Gy versus BED{sub 10} of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed. Conclusions: SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.« less

Anticancer activities of bovine and human lactoferricin-derived peptides.

PubMed

Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

2017-02-01

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

Intestinal lactoferrin receptor: presence and specificity during development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davidson, L.A.; Lonnerdal, B.L.

1986-03-01

As the major iron-binding protein in breast milk, lactoferrin (Lf) has been suggested to play a role in Fe absorption from milk. The authors previous work has validated the use of the Rhesus monkey as a model for studying this role of Lf. They have identified a specific Lf receptor on the brush border (BB) of juvenile Rhesus small intestine (s.i.) which may facilitate Fe uptake into the mucosal cell. In this study the authors examined the presence and specificity of the Lf receptor during development. BB membrane vesicles were prepared from fetal (113 d gestation), infant (3 m), andmore » adult (12 y) Rhesus s.i.; Binding assays were performed by incubating BB vesicles with 59-Fe-Lf and filtering through a 0.22 ..mu..m filter. The fetal and infant tissues were found to possess receptors with a high affinity for Lf. This early ontogeny indicates the importance of the receptor to the infant. Adult s.i. contained Lf receptors in all regions. Since the adult has no dietary intake of Lf, the receptor may play a role in Fe homeostasis via biliary Lf excretion or may simply continue to be expressed throughout life. The receptors were examined for their affinity for purified bovine Lf and human transferrin, both of which are similar in structure to Lf. No binding was found for either, demonstrating the specificity of the receptor for Lf. The presence of the Lf receptor in fetal tissue and its specificity for Lf implies it is essential for adequate Fe nutrition of the suckling infant.« less

Lysophosphatidic Acid Induces Ligamentum Flavum Hypertrophy Through the LPAR1/Akt Pathway.

PubMed

Zhou, Tangjun; Du, Lin; Chen, Chen; Han, Chen; Li, Xunlin; Qin, An; Zhao, Changqing; Zhang, Kai; Zhao, Jie

2018-01-01

Hypertrophic ligamentum flavum (LF) is a major cause of lumbar spinal stenosis. Our previous work showed that high levels of lysophosphatidic acid (LPA) expression are positively correlated with LF hypertrophy. This study aimed to further unveil how LPA regulates LF hypertrophy Methods: We studied LPAR1 expression in human LF cells using PCR and western blotting. Cell viability cell cycle, apoptosis rate and molecular mechanisms were assayed in LPAR1 knockdown or overexpression LF cells. LF hypertrophy and the molecular mechanism was confirmed in human samples and in in vivo studies. The expression of LPA and its receptor LPAR1 is significantly higher in tissues or cells harvested from hypertrophic LF compared to healthy controls. Moreover, LPA promoted LF cell proliferation by interacting with LPAR1. This conclusion is supported by the fact that depletion or overexpression of LPAR1 changed the effect of LPA on LF cell proliferation. LPA also inhibits apoptosis in LF cells through the receptor LPAR1. Importantly, we demonstrated that the LPA-LPAR1 interaction initiated Akt phosphorylation and determined cell proliferation and apoptosis. Our in vitro findings were supported by our in vivo evidence that lyophilized LPA significantly induced LF hypertrophy via the LPAR1-Akt signaling pathway. More importantly, targeted inhibition of LPAR1 by Ki16425 with a gel sponge implant effectively reduced LPA-associated LF hypertrophy. Taken together, these data indicate that LPA binds to the receptor LPAR1 to induce LF cell proliferation and inhibit apoptosis by activating AKT signaling cascades. Targeting this signaling cascade with Ki16425 is a potential therapeutic strategy for preventing LF hypertrophy. LPA-LPAR1-Akt activation is positively correlated with the proliferation and survival of LF cells. LPAR1 could be a target for new drugs and the development of new therapeutic methods for treating LF hypertrophy. © 2018 The Author(s). Published by S. Karger AG, Basel.

Factors Associated with Increased Risk for Lethal Violence in Intimate Partner Relationships among Ethnically Diverse Black Women

PubMed Central

Sabri, Bushra; Stockman, Jamila K.; Campbell, Jacquelyn C.; O’Brien, Sharon; Campbell, Doris; Callwood, Gloria B.; Bertrand, Desiree; Sutton, Lorna W.; Hart-Hyndman, Greta

2014-01-01

The purpose of this study was to identify factors associated with increased risk for lethal violence among ethnically diverse Black women in Baltimore, Maryland (MD) and the US Virgin Islands (USVI). Women with abuse experiences (n=456) were recruited from primary care, prenatal or family planning clinics in Baltimore, MD and St. Thomas and St. Croix, USVI. Logistic regression was used to examine factors associated with the risk for lethal violence among abused women. Factors independently related to increased risk of lethal violence included fear of abusive partners, PTSD symptoms, and use of legal resources. These factors must be considered in assessing safety needs of Black women in abusive relationships. PMID:25429191

[Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection].

PubMed

Hao, Li-Jun; Lin, Yan; Zhang, Wei; Tian, Jiao; Wang, Ya; Chen, Peng-De; Hu, Chong-Kang; Zeng, Ling-Chao; Yang, Jie; Wang, Bao-Xi; Jiang, Xun

2017-06-01

To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection. The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant. After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). EPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.

Human Lactoferrin and Peptides Derived from a Surface-Exposed Helical Region Reduce Experimental Escherichia coli Urinary Tract Infection in Mice

PubMed Central

Håversen, Liliana A.; Engberg, Inga; Baltzer, Lars; Dolphin, Gunnar; Hanson, Lars Å.; Mattsby-Baltzer, Inger

2000-01-01

Lactoferrin (LF) is a multifunctional immunoregulatory protein that has been associated with host defense at mucosal surfaces through its antibacterial properties. The antibacterial and anti-inflammatory properties of LF were further explored with an animal model of experimental urinary tract infection. Bovine LF (bLF), human LF (hLF), and synthetic peptide sequences based on the antibacterial region of hLF (amino acid residues 16 to 40 [HLD1] and 18 to 40 [HLD2]) were given orally to female mice 30 min after the instillation of 108 Escherichia coli bacteria into the urinary bladder. The control groups received phosphate-buffered saline or water. C3H/Tif mice were treated with hLF or bLF, and C3H/HeN mice were treated with bLF only. The numbers of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were significantly reduced 24 h later by the LF treatments compared to the findings for the control group. The hLF-treated group showed the strongest reduction compared with the vehicle-treated-group (P values were 0.009 and 0.0001 for the kidneys and bladder, respectively). The urinary leukocyte response was diminished in the hLF-treated group. The hLF treatment also significantly reduced the urinary interleukin-6 (IL-6) levels at 2 h and the systemic IL-6 levels at 24 h after infection (P values were 0.04 and < 0.002, respectively). In the bLF-treated animals, no such strong anti-inflammatory effects were obtained. In another series of experiments, C3H/Tif mice perorally treated with HLD1 or HLD2 also showed reduced numbers of bacteria in the kidneys compared with the vehicle-treated mice, although the results were significantly different only for HLD2 (P < 0.01). Analysis of urine from hLF-fed C3H/Tif mice showed that hLF was excreted into the urinary tract at 2 h after feeding. Testing of the in vitro bactericidal activity of LF (1 mg/ml) or the peptides (0.1 mg/ml) in mouse urine against the E. coli bacteria revealed moderate killing only by HLD2. In conclusion, these results demonstrate for the first time that oral administration of hLF or peptides thereof is effective in reducing infection and inflammation at a remote site, the urinary tract, possibly through transfer of hLF or its peptides to the site of infection via renal secretion. The antibacterial mechanism is suggested to involve bactericidal capacities of LF, fragments thereof, or its peptides. PMID:10992490

Nanopharmaceuticals to target antifilarials: a comprehensive review.

PubMed

Ali, Mohammad; Afzal, Mohammad; Bhattacharya, Shailja Misra; Ahmad, Farhan Jalees; Dinda, Amit Kumar

2013-05-01

Currently emphasized conventional chemotherapies for the elimination of lymphatic filariasis (LF) are imperfect due to unfocused targeting of poorly water-soluble antifilarial drugs. The profound location of drug targets (filarial parasites or wolbachia) within the complex anatomy of lymphatic tissues often necessitates prolonged treatment schedules with high doses leading to undesired side effects and poor patient compliance. Therefore, we need to reformulate antifilarial drugs taking the advantages of nanotechnology through a wide range of nanomedical carriers, which improve drug efficacy, increase bioavailability, and diminish toxicity. Connotations of drug delivery systems (DDSs) to target lymphatic filaroids or wolbachia and systemic microfilaria have been discussed. The potentials of liposomes and solid lipid nanoparticles for the treatment of LF are highlighted. Various critical factors, viz optimal size range, surface properties, preferred pH, mechanism of reticuloendothelial avoidance, and control of the release of antifilarial agents for safe elimination of parasites, are enclosed to design a novel DDS for LF. The review of nanotechnological approaches to improve antifilarial chemotherapy will help to resolve existing technological gaps. Precincts in the antifilarial discovery programs can never be overcome by conventional methods. Nanomedicine encompasses wide-range solution for each single problem (i.e., from poor solubility to nonspecific targeting of antifilarial agents) for the cure of LF at low costs and may reduce the economic burden of LF diseases. Advances in nanotechnology loom will certainly come forward as silver bullets in the near future for quick diagnosis, control, and elimination of this tropically neglected disease.

Assessment of high to low frequency variations of isoprene emission rates using a neural network approach

NASA Astrophysics Data System (ADS)

Boissard, C.; Chervier, F.; Dutot, A. L.

2007-08-01

Using a statistical approach based on artificial neural networks, an emission algorithm (ISO_LF) accounting for high (instantaneous) to low (seasonal) frequency variations was developed for isoprene. ISO_LF was optimised using an isoprene emission data base (ISO-DB) specifically designed for this work. ISO-DB consists of 1321 emission rates collected in the literature, together with 34 environmental variables, measured or assessed using NCDC (National Climatic Data Center) or NCEP (National Centers for Environmental Predictions) meteorological databases. ISO-DB covers a large variety of emitters (25 species) and environmental conditions (10° S to 60° N). When only instantaneous environmental regressors (air temperature and photosynthetic active radiation, PAR) were used, a maximum of 60% of the overall isoprene variability was assessed and the highest emissions were underestimated. Considering a total of 9 high (instantaneous) to low (up to 3 weeks) frequency regressors, ISO_LF accounts for up to 91% of the isoprene emission variability, whatever the emission range, species or climate. Diurnal and seasonal variations are correctly reproduced for textit{Ulex europaeus} with a maximum factor of discrepancy of 4. ISO-LF was found to be mainly sensitive to air temperature cumulated over 3 weeks T21 and to instantaneous light L0 and air temperature T0 variations. T21, T0 and L0 only accounts for 76% of the overall variability. The use of ISO-LF for non stored monoterpene emissions was shown to give poor results.

[The role of CD14 promoter - 159 C-> T polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diets in healthy Chinese Han youth].

PubMed

Jiang, Zhe; Gong, Ren-rong; Li, Yuan-hao; Fan, Mei; Fang, Ding-zhi

2012-05-01

To investigate the role of CD14 promoter - 159 C-> T polymorphism on ratios of serum lipids and its interaction on the ratios with a high-carbohydrate/low-fat (HC/LF) diet in a young and healthy Chinese Han population. After a washout diet for seven days, fifty six healthy young subjects (22.89 +/- 1.80 years) were given the HC/LF diet for six days. Twelve-hour fasting venous blood samples were collected in the mornings of the first, the eighth and the fourteenth days. The serum lipid profiles and the CD14 -159 C->T polymorphism were analyzed. The ratios of triglyceride/high density lipoprotein-cholesterol (TG/HDL-c), log (TG/HDL-c), total cholesterol/high density lipoprotein-cholesterol (TC/HDL-c) and low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-c/HDL-c) were calculated. The male carriers of the C allele had significantly higher TG/HDL-c and log (TG/HDL-c) than the female carriers at baseline, after the washout diet and after the HC/LF diet, higher TC/HDL-c at baseline and after the washout diet, and higher LDL-c/HDL-c only after the washout diet. The female subjects with the TT genotype had higher TG/HDL-c and log (TG/HDL-c) than the female carriers of the C allele at baseline, after the washout diet and after the HC/LF diet, higher LDL-c/HDL-c at baseline and after the HC/LF diet, and higher TC/HDL-c only after the washout diet. Compared with that before the HC/LF diet, TC/HDL-c was significantly decreased after the HC/LF diet regardless of gender and the genotype of the CD14 -159 polymorphism. LDL-c/HDL-c was significantly decreased in both the male and female carriers of the C allele. TG/HDL-c and log (TG/HDL-c) were significantly increased only in the female carriers of the C allele. In the subjects with C allele, the HC/LF diet is a minor factor and its effects on the lipid ratios can be masked by the effects of the C allele at CD14 -159. The interaction between the HC/LF diet and the C allele at CD14 -159 can decrease LDL-c/HDL-c in both males and females and increase TG/ HDL-c and log (TG/HDL-c) in the females.

A single-center randomized controlled trial observing the safety and efficacy of modified step-up graded Valsalva manoeuver in patients with vasovagal syncope

PubMed Central

Liu, Xiaoyan; Yu, Yijun; Zeng, Xiaoyun; Li, Huanhuan

2018-01-01

Non-pharmacological therapies, especially the physical maneuvers, are viewed as important and promising strategies for reducing syncope recurrences in vasovagal syncope (VVS) patients. We observed the efficacy of a modified Valsalva maneuver (MVM) in VVS patients. 72 VVS patients with syncope history and positive head-up tilt table testing (HUTT) results were randomly divided into conventional treatment group (NVM group, n = 36) and conventional treatment plus standard MVM for 30 days group (MVM group, n = 36). Incidence of recurrent syncope after 12 months (6.5% vs. 41.2%, P<0.01) and rate of positive HUTT after 30 days (9.7% vs.79.4%, P<0.01) were significantly lower in MVM group than in NVM group. HRV results showed that low frequency (LF), LF/ high frequency (HF), standard deviation of NN intervals (SDNN) and standard deviation of all 5-min average NN intervals (SDANN) values were significantly lower in the NVM and MVM groups than in the control group at baseline. After 30 days treatment, LF, LF/HF, SDNN, SDANN values were significantly higher compared to baseline in MVM group. Results of Cox proportional hazard model showed that higher SDNN and SDANN values at 30 days after intervention were protective factors, while positive HUTT at 30 days after intervention was risk factor for recurrent syncope. Our results indicate that 30 days MVM intervention could effectively reduce the incidence of recurrent syncope up to 12 months in VVS patients, possibly through improving sympathetic function of VVS patients. PMID:29381726

A single-center randomized controlled trial observing the safety and efficacy of modified step-up graded Valsalva manoeuver in patients with vasovagal syncope.

PubMed

He, Li; Wang, Lan; Li, Lun; Liu, Xiaoyan; Yu, Yijun; Zeng, Xiaoyun; Li, Huanhuan; Gu, Ye

2018-01-01

Non-pharmacological therapies, especially the physical maneuvers, are viewed as important and promising strategies for reducing syncope recurrences in vasovagal syncope (VVS) patients. We observed the efficacy of a modified Valsalva maneuver (MVM) in VVS patients. 72 VVS patients with syncope history and positive head-up tilt table testing (HUTT) results were randomly divided into conventional treatment group (NVM group, n = 36) and conventional treatment plus standard MVM for 30 days group (MVM group, n = 36). Incidence of recurrent syncope after 12 months (6.5% vs. 41.2%, P<0.01) and rate of positive HUTT after 30 days (9.7% vs.79.4%, P<0.01) were significantly lower in MVM group than in NVM group. HRV results showed that low frequency (LF), LF/ high frequency (HF), standard deviation of NN intervals (SDNN) and standard deviation of all 5-min average NN intervals (SDANN) values were significantly lower in the NVM and MVM groups than in the control group at baseline. After 30 days treatment, LF, LF/HF, SDNN, SDANN values were significantly higher compared to baseline in MVM group. Results of Cox proportional hazard model showed that higher SDNN and SDANN values at 30 days after intervention were protective factors, while positive HUTT at 30 days after intervention was risk factor for recurrent syncope. Our results indicate that 30 days MVM intervention could effectively reduce the incidence of recurrent syncope up to 12 months in VVS patients, possibly through improving sympathetic function of VVS patients.

Cupping - is it reproducible? Experiments about factors determining the vacuum.

PubMed

Huber, R; Emerich, M; Braeunig, M

2011-04-01

Cupping is a traditional method for treating pain which is investigated nowadays in clinical studies. Because the methods for producing the vacuum vary considerably we tested their reproducibility. In a first set of experiments (study 1) four methods for producing the vacuum (lighter flame 2 cm (LF1), lighter flame 4 cm (LF2), alcohol flame (AF) and mechanical suction with a balloon (BA)) have been compared in 50 trials each. The cupping glass was prepared with an outlet and stop-cock, the vacuum was measured with a pressure-gauge after the cup was set to a soft rubber pad. In a second series of experiments (study 2) we investigated the stability of pressures in 20 consecutive trials in two experienced cupping practitioners and ten beginners using method AF. In study 1 all four methods yielded consistent pressures. Large differences in magnitude were, however, observed between methods (mean pressures -200±30 hPa with LF1, -310±30 hPa with LF2, -560±30 hPa with AF, and -270±16 hPa with BA). With method BA the standard deviation was reduced by a factor 2 compared to the flame methods. In study 2 beginners had considerably more difficulty obtaining a stable pressure yield than advanced cupping practitioners, showing a distinct learning curve before reaching expertise levels after about 10-20 trials. Cupping is reproducible if the exact method is described in detail. Mechanical suction with a balloon has the best reproducibility. Beginners need at least 10-20 trials to produce stable pressures. Copyright © 2010 Elsevier Ltd. All rights reserved.

Lactoferrin Expression in Human and Murine Ocular Tissue.

PubMed

Rageh, Abrar A; Ferrington, Deborah A; Roehrich, Heidi; Yuan, Ching; Terluk, Marcia R; Nelson, Elizabeth F; Montezuma, Sandra R

2016-07-01

Lactoferrin (LF) is a multifunctional protein known to provide innate defense due to its antimicrobial and anti-inflammatory properties. In the eye, LF has been identified in the tears and vitreous humor. Its presence in other ocular tissues has not been determined. Our aim is to assess the presence of LF in the cornea, iris, retina and retinal pigment epithelium (RPE) of humans and mice. To test for the endogenous production of LF, reverse transcription polymerase chain reaction was performed in cultured human cells from the cornea and RPE and in murine tissues. To confirm LF localization in specific ocular tissue, immunohistochemistry was performed on flat mounts of cornea, retina and RPE in human donor eyes. The presence of LF was assessed by western blotting in human and mouse ocular tissue and human culture cells (cornea and RPE). To verify antibody specificity, purified human LF and transferrin (TF) were used on 1D and 2D western blots. LF gene expression was confirmed in the cornea and RPE cell cultures from humans, suggesting that LF is an endogenously produced protein. PCR results from mouse ocular tissue showed LF expression in cornea, iris, RPE, but not in retina. These results were also consistent with immunohistochemical localization of LF in human donor tissue. Antibody reaction for human LF was specific and western blotting showed its presence in the cornea, iris and RPE tissues. A faint reaction for the retina was observed but was likely due to contamination from other ocular tissues. Multiple commercially available antibodies for murine LF cross-reacted with TF, so no reliable results were obtained for murine western blot. LF is expressed in multiple eye tissues of humans and mice. This widespread expression and multifunctional activity of LF suggests that it may play an important role in protecting eye tissues from inflammation-associated diseases.

A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

PubMed

Meng, Fanfei; Asghar, Sajid; Gao, Shiya; Su, Zhigui; Song, Jue; Huo, Meirong; Meng, Weidong; Ping, Qineng; Xiao, Yanyu

2015-10-01

In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibitory Effects of Lactoferrin on Growth and Biofilm Formation of Porphyromonas gingivalis and Prevotella intermedia▿

PubMed Central

Wakabayashi, Hiroyuki; Yamauchi, Koji; Kobayashi, Tetsuo; Yaeshima, Tomoko; Iwatsuki, Keiji; Yoshie, Hiromasa

2009-01-01

Lactoferrin (LF) is an iron-binding antimicrobial protein present in saliva and gingival crevicular fluids, and it is possibly associated with host defense against oral pathogens, including periodontopathic bacteria. In the present study, we evaluated the in vitro effects of LF-related agents on the growth and biofilm formation of two periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, which reside as biofilms in the subgingival plaque. The planktonic growth of P. gingivalis and P. intermedia was suppressed for up to 5 h by incubation with ≥130 μg/ml of human LF (hLF), iron-free and iron-saturated bovine LF (apo-bLF and holo-bLF, respectively), and ≥6 μg/ml of bLF-derived antimicrobial peptide lactoferricin B (LFcin B); but those effects were weak after 8 h. The biofilm formation of P. gingivalis and P. intermedia over 24 h was effectively inhibited by lower concentrations (≥8 μg/ml) of various iron-bound forms (the apo, native, and holo forms) of bLF and hLF but not LFcin B. A preformed biofilm of P. gingivalis and P. intermedia was also reduced by incubation with various iron-bound bLFs, hLF, and LFcin B for 5 h. In an examination of the effectiveness of native bLF when it was used in combination with four antibiotics, it was found that treatment with ciprofloxacin, clarithromycin, and minocycline in combination with native bLF for 24 h reduced the amount of a preformed biofilm of P. gingivalis compared with the level of reduction achieved with each agent alone. These results demonstrate the antibiofilm activity of LF with lower iron dependency against P. gingivalis and P. intermedia and the potential usefulness of LF for the prevention and treatment of periodontal diseases and as adjunct therapy for periodontal diseases. PMID:19451301

Comparison of the larynx-associated lymphoid tissue in the false vocal cords and subglottis in pediatric autopsies.

PubMed

Rossi e Silva, Renata Calciolari; Olegário, Janainna Grazielle Pacheco; Abate, Débora Tavares de Rezende e Silva; Salge, Ana Karina Marques; Peres, Luiz César; Corrêa, Rosana Rosa Miranda; Castro, Eumenia Costa da Cunha; Teixeira, Vicente de Paula Antunes

2012-12-15

The aim this work was to compare the distribution of cellular phenotypes of the LF in the FVC to the ones in the subglottic region in pediatric autopsy, relating this distribution to age and different causes of death. We analyzed 60 larynges of newborns and children autopsied in the period from 1993 to 2003. The fragments were prepared in order to perform histochemical and immunohistochemical techniques. The morphological analysis showed cases that presented LF only in FVC (35%), LF only in the subglottic region (20%), lack of LF in FVC (30%) and lymphoid aggregates, which did not characterize an LF (15%). The cases of LF in the subglottic region were significantly younger compared to the ones that presented LF in the FVC (p=0.017). The LF in the subglottic region was bigger than the LF in the FVC (p=0.020). There was no significant difference between the cause of death and cellular phenotype for both FVC and the subglottic region. In conclusion, the cells that make up the LF in the FVC in newborns and children younger than one year have functional characteristics similar to LF cells in the subglottic region, suggesting that there are similarities with LALT. Copyright © 2012 Elsevier GmbH. All rights reserved.

Lactoferrin delivery systems: approaches for its more effective use.

PubMed

Onishi, Hiraku

2011-11-01

Recently, pharmacotherapy has advanced extensively, but there are still many refractory diseases which cannot be solved fully by existing therapeutic agents. Therefore, alternative medicine and health foods are now attracting much attention, for example, lactoferrin (LF): a multifunctional glycoprotein. As LF is non-toxic and low-cost, its application in healthcare and therapeutics is expected to be widespread. In this review, LF's general basic features are described. The interaction of LF with its receptors activates the immune system, including cytokine production and balance. In particular, the immune activation of orally administered LF is considered as a new strategy for the treatment of refractory diseases, such as inflammatory bowel disease, virus infection and tumor metastasis. Also mentioned are the problems associated with the use of LF. As LF is degraded rapidly in the body due to enzymatic hydrolysis, high amounts or frequent dosing is required; an appropriate delivery system may improve these problems and increase its efficiency. Chemical modifications, such as PEGylation, can enhance the stability of LF in the body, resulting in increased efficacy. Also, liposomes and enteric or microparticulate formulations can promote the function of LF in oral administration due to target site delivery and protection of LF from enzymatic hydrolysis. These delivery systems are expected to improve the utility of LF.

The dominant expression of functional human lactoferrin in transgenic cloned goats using a hybrid lactoferrin expression construct.

PubMed

Yu, Huiqing; Chen, Jianquan; Sun, Wei; Liu, Siguo; Zhang, Aimin; Xu, Xujun; Wang, Xuebin; He, Zhuzi; Liu, Guohui; Cheng, Guoxiang

2012-10-31

Human Lactoferrin (hLF) is an iron-binding protein with multiple physiological functions. As the availability of natural hLF is limited, alternative means of producing this biopharmaceutical protein have been extensively studied. Here we report on the dominant expression of recombinant human lactoferrin (rhLF) in transgenic cloned goats using a novel optimised construct made by fusing a 3.3 kb hLF minigene to the regulatory elements of the β-casein gene. The transgenic goat produced more than 30 mg/ml rhLF in its milk, and rhLF expression was stable during the entire lactation cycle. The rhLF purification efficiency from whole goat milk is approximately 70%, and its purity is above 98%. Compared with natural hLF, the rhLF from transgenic goats has similar biological characteristics including molecular mass, N-terminal sequence, isoelectric point, immunoreactivity and digestive stability. More importantly, the purified rhLF showed specific anti-tumour activity in the mouse model of melanoma experimental metastasis. Therefore, our study shows that the large-scale production of functional rhLF in transgenic goat milk could be an economical and promising source of human therapeutic use in the future. Copyright © 2012. Published by Elsevier B.V.

Comparison of Adverse Events and Hospital Length of Stay Associated With Various Amphotericin B Formulations

PubMed Central

Wade, Rolin L.; Chaudhari, Paresh; Natoli, Jaime L.; Taylor, Robert J.; Nathanson, Brian H.; Horn, David

2013-01-01

Purpose: Patients with invasive fungal infections are often treated initially with conventional amphotericin B deoxycholate (CAB), followed by a switch to lipid-based formulations of amphotericin B (LF-AMB). Our study examined adverse events and hospital length of stay (LOS) among adults who received LF-AMB exclusively or CAB followed by LF-AMB (CAB/LF-AMB). Methods: Data were extracted from the Cerner Health Facts database. The study included adults with evidence of infection by Aspergillus, Candida, or Cryptococcus in addition to either renal insufficiency, a clinical condition suggesting intolerance to CAB, or CAB exposure within 90 days of admission. Nephrotoxicity was defined as a serum creatinine (SCr) level exceeding a 100% increase from baseline and an absolute level above 1.2 mg/dL. We used a hierarchical mixed-effect logistic regression model with nephrotoxicity as the outcome for the multivariate analysis. Results: The study included 327 LF-AMB and 81 CAB/LF-AMB patients with similar demographics and baseline SCr values. The mean pre-to-post percentage increase in SCr levels was greater for CAB/LF-AMB (122.9%) compared with LF-AMB (62.2%) (P < 0.001). The multivariate-adjusted odds ratio of nephrotoxicity was 5.93, for a 95% confidence interval of 2.92 to 12.05 (P < 0.001) for CAB/LF-AMB compared with LF-AMB. Hypokalemia, hypomagnesemia, and infusion-related reactions were more frequent with CAB/LF-AMB. Compared with the LF-AMB group, the CAB/LF-AMB patients had a longer post-amphotericin B LOS (24.1 days vs. 15.7 days, respectively; P < 0.001), with a marginal effect of 4.5 days longer for those receiving CAB/LF-AMB (P = 0.016). Conclusion: In this retrospective study, we noted a significantly longer post-amphotericin B LOS and a greater frequency of adverse events, including nephrotoxicity, for patients whose initial treatment was CAB and who were switched to LF-AMB, compared with patients who received LF-AMB only. PMID:23946621

An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following a high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial.

PubMed

Campbell, Matthew D; Walker, Mark; Ajjan, Ramzi A; Birch, Karen M; Gonzalez, Javier T; West, Daniel J

2017-07-01

To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. A total of 10 males with type 1 diabetes [HbA 1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-h post-meal and analysed for triglyceride, non-esterified-fatty acids, apolipoprotein B48, glucagon, tumour necrosis factor alpha, fibrinogen, human tissue factor activity and plasminogen activator inhibitor-1. Continuous glucose monitoring captured interstitial glucose responses. Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions. Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.

Influence of level and duration of feeding polysaccharide (laminarin and fucoidan) extracts from brown seaweed (Laminaria digitata) on quality indices of fresh pork.

PubMed

Moroney, N C; O'Grady, M N; Robertson, R C; Stanton, C; O'Doherty, J V; Kerry, J P

2015-01-01

The effect of level (450 or 900 mg laminarin (L) and fucoidan (F) /kg feed) and duration (3 or 6 wks) of feeding a seaweed (Laminaria digitata) extract containing L/F on the quality of pork (longissimus thoracis et lumborum (LTL)) stored in modified atmosphere packs and on organ lipid stability was examined. Mechanisms of L/F antioxidant activity in LTL were evaluated. Plasma total antioxidant status, LTL pH, colour, microbiology and 'eating quality' sensory analysis were unaffected by dietary L/F. 'Visual' sensory descriptors (purchasing appeal and overall visual acceptability) were enhanced (p<0.05) in L/F450-3 LTL. Lipid oxidation was lower (p<0.05) in L/F450-3 and L/F900-3 LTL and reduced in L/F900-6 kidney homogenates. In cooked minced pork, lipid oxidation was not reduced by dietary L/F. Saturated fatty acids were lower (p<0.05) in L/F900-6 LTL. Results indicated L/F in pig diets for 3 weeks enhanced pork quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

Short Segment Spinal Instrumentation With Index Vertebra Pedicle Screw Placement for Pathologies Involving the Anterior and Middle Vertebral Column Is as Effective as Long Segment Stabilization With Cage Reconstruction: A Biomechanical Study.

PubMed

Bartanusz, Viktor; Harris, Jonathan; Moldavsky, Mark; Cai, Yiwei; Bucklen, Brandon

2015-11-01

An in vitro, cadaveric biomechanical study. The aim of the present study was to compare single-segment posterior instrumentation and fracture-level screws with single/multilevel posterior fixation and corpectomy in a simulated, unstable burst fracture model. The optimal extent of instrumentation for surgical cases of non-neoplastic vertebral body pathologies remains uncertain. Although several clinical studies demonstrate advantages of short segment instrumentation with index-level screws over more extensive corpectomy and anterior-posterior techniques, a comprehensive biomechanical comparison of these techniques is currently lacking. Six bovine spines (T11-L5) were tested in flexion, extension, lateral bending (LB), and axial rotation (AR) following simulated burst fracture at L2. Posterior instrumentation included 1 level above/below (1LF) and 2 levels above/below fracture level (2LF), intermediate or index screws at fracture level (FF), and cross-connectors above/below fracture level (CC). Anterior corpectomy devices included expandable corpectomy spacers with/without integrated screws, ACDi and ACD, respectively FORTIFY-Integrated/FORTIFY; Globus Medical, Inc., PA. Constructs were tested in the following order: (1) Intact; (2) 1LF; (3) 1LF and CC; (4) 1LF and FF; (5) 1LF, CC, and FF; (6) 2LF; (7) 2LF and CC; (8) 2LF and FF; (9) 2LF, CC, and FF; (10) 2LF and ACD; (11) 2LF, ACD, and CC; (12) 1LF and ACDi; (13) 1LF, ACDi, and CC. During flexion, all constructs except 1LF reduced motion relative to intact (P ≤ 0.05). Anterior support was most stable, but no differences were found between constructs (P ≥ 0.05). Every construct reduced motion in extension, though no differences were found between constructs and intact (P ≥ 0.05). During LB, all constructs reduced motion relative to intact (P ≤ 0.05); 2LF constructs further reduced motion (P ≤ 0.05). No construct returned AR motion to intact, with significant increases in 1LF and ACDi, 2LF and ACD, and 2LF, ACD, and CC (P ≤ 0.05). Cross-connectors and fracture screws reinforced each other in posterior-only constructs, providing maximum stability (P ≥ 0.05). This biomechanical comparison study found no significant superiority of combined anterior-posterior constructs over short segment fracture screw fixation, only multilevel posterior instrumentation with and without anterior support, providing increased stability in LB. Biomechanical equivalency suggests that short segment fracture screw intervention may provide appropriate stabilization for non-neoplastic pathologies involving the anterior and middle vertebral columns. 2.

Binding and Endocytosis of Bovine Hololactoferrin by the Parasite Entamoeba histolytica.

PubMed

Ortíz-Estrada, Guillermo; Calderón-Salinas, Víctor; Shibayama-Salas, Mineko; León-Sicairos, Nidia; de la Garza, Mireya

2015-01-01

Entamoeba histolytica is a human parasite that requires iron (Fe) for its metabolic function and virulence. Bovine lactoferrin (B-Lf) and its peptides can be found in the digestive tract after dairy products are ingested. The aim of this study was to compare virulent trophozoites recently isolated from hamster liver abscesses with nonvirulent trophozoites maintained for more than 30 years in cultures in vitro regarding their interaction with iron-charged B-Lf (B-holo-Lf). We performed growth kinetics analyses of trophozoites in B-holo-Lf and throughout several consecutive transfers. The virulent parasites showed higher growth and tolerance to iron than nonvirulent parasites. Both amoeba variants specifically bound B-holo-Lf with a similar K d . However, averages of 9.45 × 10(5) and 6.65 × 10(6) binding sites/cell were found for B-holo-Lf in nonvirulent and virulent amoebae, respectively. Virulent amoebae bound more efficiently to human and bovine holo-Lf, human holo-transferrin, and human and bovine hemoglobin than nonvirulent amoebae. Virulent amoebae showed two types of B-holo-Lf binding proteins. Although both amoebae endocytosed this glycoprotein through clathrin-coated vesicles, the virulent amoebae also endocytosed B-holo-Lf through a cholesterol-dependent mechanism. Both amoeba variants secreted cysteine proteases cleaving B-holo-Lf. These data demonstrate that the B-Lf endocytosis is more efficient in virulent amoebae.

Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups.

PubMed

Nourdin-Galindo, Guillermo; Sánchez, Patricio; Molina, Cristian F; Espinoza-Rojas, Daniela A; Oliver, Cristian; Ruiz, Pamela; Vargas-Chacoff, Luis; Cárcamo, Juan G; Figueroa, Jaime E; Mancilla, Marcos; Maracaja-Coutinho, Vinicius; Yañez, Alejandro J

2017-01-01

Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis , functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these genes could be directly associated with inter-genogroup differences in pathogenesis and host-pathogen interactions, information that could be useful in designing novel strategies for diagnosing and controlling P. salmonis infection.

Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups

PubMed Central

Nourdin-Galindo, Guillermo; Sánchez, Patricio; Molina, Cristian F.; Espinoza-Rojas, Daniela A.; Oliver, Cristian; Ruiz, Pamela; Vargas-Chacoff, Luis; Cárcamo, Juan G.; Figueroa, Jaime E.; Mancilla, Marcos; Maracaja-Coutinho, Vinicius; Yañez, Alejandro J.

2017-01-01

Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these genes could be directly associated with inter-genogroup differences in pathogenesis and host-pathogen interactions, information that could be useful in designing novel strategies for diagnosing and controlling P. salmonis infection. PMID:29164068

A novel heart rate control model provides insights linking LF-HRV behavior to the open-loop gain.

PubMed

Dvir, Hila; Bobrovsky, Ben Zion; Gabbay, Uri

2013-09-20

Low-frequency heart rate variability (LF-HRV) at rest has already been successfully modeled as self-sustained oscillations in a nonlinear control loop, but these models fail to simulate LF-HRV decreases either during aerobic exercise or in heart failure patients. Following control engineering practices, we assume the existence of a biological excitation (dither) within the heart rate control loop that softens the nonlinearity and studied LF-HRV behavior in a dither-embedded model. We adopted the Ottesen model with some revisions and induced a dither of high-frequency stochastic perturbations. We simulated scenarios of a healthy subject at rest and during aerobic exercise (by decreasing peripheral vascular resistance) and a heart failure patient (by decreasing stroke volume). The simulations resembled physiological LF-HRV behavior, i.e., LF-HRV decreased during aerobic exercise and in the heart failure patient. The simulations exhibited LF-HRV dependency on the open-loop gain, which is related to the product of the feedback gain and the feed forward gain. We are the first to demonstrate that LF-HRV may be dependent on the open-loop gain. Accordingly, reduced open-loop gain results in decreased LF-HRV, and vice versa. Our findings explain a well-known but unexplained observed phenomenon of reduced LF-HRV both in heart failure patients and in healthy subjects performing aerobic exercise. These findings have implications on how changes in LF-HRV can be interpreted physiologically, a necessary step towards the clinical utilization of LF-HRV. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Physicochemical properties of β-carotene emulsions stabilized by chlorogenic acid-lactoferrin-glucose/polydextrose conjugates.

PubMed

Liu, Fuguo; Wang, Di; Xu, Honggao; Sun, Cuixia; Gao, Yanxiang

2016-04-01

In this study, the influence of chlorogenic acid (CA)-lactoferrin (LF)-glucose (Glc) conjugate and CA-LF-polydextrose (PD) conjugate on the physicochemical characteristics of β-carotene emulsions was investigated. Novel emulsifiers were formed during Maillard reaction between CA-LF conjugate and Glc/PD. The physicochemical properties of β-carotene emulsions were characterized by droplet size, ζ-potential, rheological behavior, transmission changes during centrifugal sedimentation and β-carotene degradation. Results showed that the covalent attachment of Glc or PD to CA-LF conjugate effectively increased the hydrophilicity of the oil droplets surfaces and strengthened the steric repulsion between the oil droplets. Glucose was better than polydextrose for the conjugation with CA-LF conjugate to stabilize β-carotene emulsions. In comparison with LF and CA-LF-Glc/PD mixtures, CA-LF-Glc/PD ternary conjugates exhibited better emulsifying properties and improved physical stability of β-carotene emulsions during the freeze-thaw treatment. In addition, CA-LF-Glc/PD conjugates significantly enhanced chemical stability of β-carotene in the emulsions against ultraviolet light exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prospects for Detecting Gravitational Waves at 5 Hz with Ground-Based Detectors.

PubMed

Yu, Hang; Martynov, Denis; Vitale, Salvatore; Evans, Matthew; Shoemaker, David; Barr, Bryan; Hammond, Giles; Hild, Stefan; Hough, James; Huttner, Sabina; Rowan, Sheila; Sorazu, Borja; Carbone, Ludovico; Freise, Andreas; Mow-Lowry, Conor; Dooley, Katherine L; Fulda, Paul; Grote, Hartmut; Sigg, Daniel

2018-04-06

We propose an upgrade to Advanced LIGO (aLIGO), named LIGO-LF, that focuses on improving the sensitivity in the 5-30 Hz low-frequency band, and we explore the upgrade's astrophysical applications. We present a comprehensive study of the detector's technical noises and show that with technologies currently under development, such as interferometrically sensed seismometers and balanced-homodyne readout, LIGO-LF can reach the fundamental limits set by quantum and thermal noises down to 5 Hz. These technologies are also directly applicable to the future generation of detectors. We go on to consider this upgrade's implications for the astrophysical output of an aLIGO-like detector. A single LIGO-LF can detect mergers of stellar-mass black holes (BHs) out to a redshift of z≃6 and would be sensitive to intermediate-mass black holes up to 2000  M_{⊙}. The detection rate of merging BHs will increase by a factor of 18 compared to aLIGO. Additionally, for a given source the chirp mass and total mass can be constrained 2 times better than aLIGO and the effective spin 3-5 times better than aLIGO. Furthermore, LIGO-LF enables the localization of coalescing binary neutron stars with an uncertainty solid angle 10 times smaller than that of aLIGO at 30 Hz and 4 times smaller when the entire signal is used. LIGO-LF also significantly enhances the probability of detecting other astrophysical phenomena including the tidal excitation of neutron star r modes and the gravitational memory effects.

Prospects for Detecting Gravitational Waves at 5 Hz with Ground-Based Detectors

NASA Astrophysics Data System (ADS)

Yu, Hang; Martynov, Denis; Vitale, Salvatore; Evans, Matthew; Shoemaker, David; Barr, Bryan; Hammond, Giles; Hild, Stefan; Hough, James; Huttner, Sabina; Rowan, Sheila; Sorazu, Borja; Carbone, Ludovico; Freise, Andreas; Mow-Lowry, Conor; Dooley, Katherine L.; Fulda, Paul; Grote, Hartmut; Sigg, Daniel

2018-04-01

We propose an upgrade to Advanced LIGO (aLIGO), named LIGO-LF, that focuses on improving the sensitivity in the 5-30 Hz low-frequency band, and we explore the upgrade's astrophysical applications. We present a comprehensive study of the detector's technical noises and show that with technologies currently under development, such as interferometrically sensed seismometers and balanced-homodyne readout, LIGO-LF can reach the fundamental limits set by quantum and thermal noises down to 5 Hz. These technologies are also directly applicable to the future generation of detectors. We go on to consider this upgrade's implications for the astrophysical output of an aLIGO-like detector. A single LIGO-LF can detect mergers of stellar-mass black holes (BHs) out to a redshift of z ≃6 and would be sensitive to intermediate-mass black holes up to 2000 M⊙. The detection rate of merging BHs will increase by a factor of 18 compared to aLIGO. Additionally, for a given source the chirp mass and total mass can be constrained 2 times better than aLIGO and the effective spin 3-5 times better than aLIGO. Furthermore, LIGO-LF enables the localization of coalescing binary neutron stars with an uncertainty solid angle 10 times smaller than that of aLIGO at 30 Hz and 4 times smaller when the entire signal is used. LIGO-LF also significantly enhances the probability of detecting other astrophysical phenomena including the tidal excitation of neutron star r modes and the gravitational memory effects.

Conditional recall and the frequency effect in the serial recall task: an examination of item-to-item associativity.

PubMed

Miller, Leonie M; Roodenrys, Steven

2012-11-01

The frequency effect in short-term serial recall is influenced by the composition of lists. In pure lists, a robust advantage in the recall of high-frequency (HF) words is observed, yet in alternating mixed lists, HF and low-frequency (LF) words are recalled equally well. It has been argued that the preexisting associations between all list items determine a single, global level of supportive activation that assists item recall. Preexisting associations between items are assumed to be a function of language co-occurrence; HF-HF associations are high, LF-LF associations are low, and mixed associations are intermediate in activation strength. This account, however, is based on results when alternating lists with equal numbers of HF and LF words were used. It is possible that directional association between adjacent list items is responsible for the recall patterns reported. In the present experiment, the recall of three forms of mixed lists-those with equal numbers of HF and LF items and pure lists-was examined to test the extent to which item-to-item associations are present in serial recall. Furthermore, conditional probabilities were used to examine more closely the evidence for a contribution, since correct-in-position scoring may mask recall that is dependent on the recall of prior items. The results suggest that an item-to-item effect is clearly present for early but not late list items, and they implicate an additional factor, perhaps the availability of resources at output, in the recall of late list items.

Hanging drop monoculture for selection of optimal antioxidants during in vitro maturation of porcine oocytes.

PubMed

Ishikawa, S; Machida, R; Hiraga, K; Hiradate, Y; Suda, Y; Tanemura, K

2014-04-01

We analysed the effect of three antioxidants that have different functional mechanisms on the in vitro maturation (IVM) of porcine oocytes. Single oocyte monoculture using the hanging drop (HD) system has some advantages such as improving analysis efficiency brought by the smaller number of samples than the number of oocytes cultured in one drop. Direct effects of ligands on single oocytes could also be detected without considering the effects of paracrine factors from other oocytes. After 22 h of pre-culture, denuded oocytes were cultured for 22 h with 0.01 and 0.1 μg/ml of L-carnitine (LC), lactoferrin (LF) or sulforaphane (SF) in the presence/non-presence of oxidant stress induced by H2O2 supplementation to evaluate the reducing effects against oxidative stress on nuclear maturation. As a result, compared with LC and SF, LF showed effective reduction in oxidative stress at a lower concentration (0.01 μg/ml), suggesting that LF is a more effective antioxidant in porcine oocyte IVM. Additionally, LF also increased maturation rate even in culture without H2O2. Our results clearly suggest that the HD monoculture system is useful for screening the substances that affect porcine oocyte culture. © 2014 Blackwell Verlag GmbH.

Lifestyle and dietary factors in the prevention of lethal prostate cancer

PubMed Central

Wilson, Kathryn M; Giovannucci, Edward L; Mucci, Lorelei A

2012-01-01

The prevention of lethal prostate cancer is a critical public health challenge that would improve health and reduce suffering from this disease. In this review, we discuss the evidence surrounding specific lifestyle and dietary factors in the prevention of lethal prostate cancer. We present a summary of evidence for the following selected behavioral risk factors: obesity and weight change, physical activity, smoking, antioxidant intake, vitamin D and calcium, and coffee intake. PMID:22504869

[Development and comparative evaluation of up-converting phosphor technology based lateral flow assay for rapid detection of Yersinia pestis, Bacillus anthracis spore and Brucella spp].

PubMed

Li, Chunfeng; Zhang, Pingping; Wang, Xiaoying; Liu, Xiao; Zhao, Yong; Sun, Chongyun; Wang, Chengbin; Yang, Ruifu; Zhou, Lei

2015-01-01

To develop an up-converting phosphor technology based lateral flow (UPT-LF) assay for rapid and quantitative detection of Yersinia pestis, Bacillus anthracis spore and Brucella spp.and make the comparison with BioThreat Alert (BTA) test strips (Tetracore Inc., USA). Using up-converting phosphor nano-particles (UCP-NPs) as the bio-marker, three double-antibody-sandwich model based UPT-LF strips including Plague-UPT-LF, Anthrax-UPT-LF, Brucella-UPT-LF were prepared and its sensitivity, accuracy, linearity and specificity were determined by detecting 10(10), 10(9), 10(8), 10(7), 10(6), 10(5) and 0 CFU/ml series of concentrations of Y.pestis, B.anthracis, Brucella standards and other 27 kinds of 10(9) CFU/ml series of contrations of bacteria strains.Furthermore, the speed, sensitivity and accuracy of bacteria standards and simulated sample detection were compared between UPT-LF and BTA system. The detection limit of Plague-UPT-LF, Anthrax-UPT-LF and Brucella-LF was 10(5) CFU/ml. The CV of series of bacteria concentrations was ≤ 15%, and the r between lg (T/C-cut-off) and lg (concentration) was 0.996,0.998 and 0.999 (F values were 1 647.57, 743.51 and 1 822.17. All the P values were <0.001), respectively. The specificity of Plague-UPT-LF and Brucella-LF were excellent, while that of Anthrax-UPT-LF was a little bit regretful because of non-specific reaction with two isolates of B. subtilis and one B.cereus. On-site evaluation showed the detection time of UPT-LF for all Y.pestis, B.anthracis spore and Brucella spp.was 33, 36 and 37 min, while BTA was 115, 115 and 111 min, which revealed the higher detection speed and sensitivity of UPT-LF comparing with BTA. The negative rate of two methods for blank standard was both 5/5, the sensitivity of UPT-LF for Y.pestis,B.anthracis spore and Brucella spp. was all 10(5) CFU/ml, then BTA was 10(6), 10(6) and 10(5) CFU/ml, respectively. The detection rate of UPT-LF for all three bacteria analog positive samples was 16/16, while BTA for B.anthracis was 7/16 only. The good performance including rapidness, simplicity and high sensitivity will bring the bright future of UPT-LF to be broadly used on-site as first response to bio-terrorism.

A TALE OF DWARFS AND GIANTS: USING A z = 1.62 CLUSTER TO UNDERSTAND HOW THE RED SEQUENCE GREW OVER THE LAST 9.5 BILLION YEARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudnick, Gregory H.; Tran, Kim-Vy; Papovich, Casey

2012-08-10

We study the red sequence in a cluster of galaxies at z = 1.62 and follow its evolution over the intervening 9.5 Gyr to the present day. Using deep YJK{sub s} imaging with the HAWK-I instrument on the Very Large Telescope, we identify a tight red sequence and construct its rest-frame i-band luminosity function (LF). There is a marked deficit of faint red galaxies in the cluster that causes a turnover in the LF. We compare the red-sequence LF to that for clusters at z < 0.8, correcting the luminosities for passive evolution. The shape of the cluster red-sequence LFmore » does not evolve between z = 1.62 and z = 0.6 but at z < 0.6 the faint population builds up significantly. Meanwhile, between z = 1.62 and 0.6 the inferred total light on the red sequence grows by a factor of {approx}2 and the bright end of the LF becomes more populated. We construct a simple model for red-sequence evolution that grows the red sequence in total luminosity and matches the constant LF shape at z > 0.6. In this model the cluster accretes blue galaxies from the field whose star formation is quenched and who are subsequently allowed to merge. We find that three to four mergers among cluster galaxies during the 4 Gyr between z = 1.62 and z = 0.6 match the observed LF evolution between the two redshifts. The inferred merger rate is consistent with other studies of this cluster. Our result supports the picture that galaxy merging during the major growth phase of massive clusters is an important process in shaping the red-sequence population at all luminosities.« less

Significant antibacterial activity and synergistic effects of camel lactoferrin with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Redwan, Elrashdy M; El-Baky, Nawal Abd; Al-Hejin, Ahmed M; Baeshen, Mohammed N; Almehdar, Hussein A; Elsaway, Abdulrahman; Gomaa, Abu-Bakr M; Al-Masaudi, Saad Berki; Al-Fassi, Fahad A; AbuZeid, Isam Eldin; Uversky, Vladimir N

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) causes major healthcare problems in many countries, as it is present as several hospital- and community-associated strains. Hospital-associated MRSA is one of the most prevalent nosocomial pathogens throughout the world and infections caused by community-acquired MRSA are rising. This emphasizes the need for new and efficient anti-MRSA agents. We evaluated the antibacterial effects of camel lactoferrin (cLf) and human lactoferrin (hLf) alone and in combination with several antibiotics against MRSA. Antimicrobials were tested against MRSA and an S. aureus control strain by the agar disc diffusion method. The minimum inhibitory concentration (MIC) was determined for antimicrobials by the broth microdilution method. Synergy between cLf or hLf and antibiotics was examined by checkerboard and time-kill assays. The agar disc diffusion assay showed that MRSA growth was inhibited by cLf at 0.25-3 mg/ml and hLf at 1-3 mg/ml. cLf demonstrated 3 times higher inhibitory activity against MRSA than hLf in terms of MIC values (250 vs. 750 μg/ml, respectively). Biotinylated cLf was recognized by two membrane proteins of MRSA, 66-67 KDa. Combinations of cLf or hLf and oxacillin or vancomycin at sub-MIC levels enhanced in vitro antibacterial activity against MRSA compared with each agent alone. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Post-Traumatic Stress Disorder, Depression, and Heart-Rate Variability among North Korean Defectors

PubMed Central

Song, Byoung-A; Yoo, So-Young; Kang, Hee-Young; Byeon, Seong-Hye; Shin, Sang-Ho; Hwang, Eun-Jeong

2011-01-01

Objective This study evaluated the symptoms of post-traumatic stress disorder (PTSD) among North Korean defectors and their level of suicidal ideation and the correlation between these and heart-rate variability (HRV) to explore the possibility of using HRV as an objective neurobiological index of signs of autonomic nervous system disorder. Methods A total of 32 North Korean defectors (nine men, 23 women) were selected as subjects, and their HRV was measured after they completed the Minnesota Multiphasic Personality Inventory-PTSD (MMPI-PTSD) scale and the Beck Depression Inventory (BDI). Results 1) Low-frequency (LF)/high-frequency (HF) ratios in the HRV index and MMPI-PTSD scores were correlated (r=0.419, p<0.05), as were BDI item 9 (suicidal ideation) and MMPI-PTSD scores (r=0.600, p<0.01). 2) A regression analysis of LF/HF ratios and MMPI-PTSD scores revealed an R-value of 13.8% (Adj. R2=0.138, F=4.695, p=0.041), and a regression analysis of BDI item 9 and MMPI-PTSD scores showed an R-value of 32.8% (Adj. R2=0.328, F=11.234, p=0.003). In other words, the LF/HF ratio (β=0.419) and BDI item 9 (β=0.600) appear to be risk factors in predicting MMPI-PTSD scores. Conclusion The LF/HF ratio, a standard index of autonomic nervous system activity, can be used as an objective neurobiological index to analyze PTSD among North Korean defectors presenting with various mental and physical symptoms, and the approximate level of suicide -ideation can act as a predicting factor for PTSD. PMID:22216038

Fibroblast growth factor signaling in myofibroblasts differs from lipofibroblasts during alveolar septation in mice

PubMed Central

McCoy, Diann M.

2015-01-01

Pulmonary alveolar fibroblasts produce extracellular matrix in a temporally and spatially regulated pattern to yield a durable yet pliable gas-exchange surface. Proliferation ensures a sufficient complement of cells, but they must differentiate into functionally distinct subtypes: contractile myofibroblasts (MF), which generate elastin and regulate air-flow at the alveolar ducts, and, in mice and rats, lipofibroblasts (LF), which store neutral lipids. PDGF-A is required but acts in conjunction with other differentiation factors arising from adjacent epithelia or within fibroblasts. We hypothesized that FGF receptor (FGFR) expression and function vary for MF and LF and contributes to their divergent differentiation. Whereas approximately half of the FGFR3 was extracellular in MF, FGFR2 and FGFR4 were primarily intracellular. Intracellular FGFR3 localized to the multivesicular body, and its abundance may be modified by Sprouty and interaction with heat shock protein-90. FGF18 mRNA is more abundant in MF, whereas FGF10 mRNA predominated in LF, which also express FGFR1 IIIb, a receptor for FGF10. FGF18 diminished fibroblast proliferation and was chemotactic for cultured fibroblasts. Although PDGF receptor-α (PDGFR-α) primarily signals through phosphoinositide 3-kinase and Akt, p42/p44 MAP kinase (Erk1/2), a major signaling pathway for FGFRs, influenced the abundance of cell-surface PDGFR-α. Observing different FGFR and ligand profiles in MF and LF is consistent with their divergent differentiation although both subpopulations express PDGFR-α. These studies also emphasize the importance of particular cellular locations of FGFR3 and PDGFR-α, which may modify their effects during alveolar development or repair. PMID:26138642

Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization.

PubMed

Tang, L; Wu, J J; Ma, Q; Cui, T; Andreopoulos, F M; Gil, J; Valdes, J; Davis, S C; Li, J

2010-07-01

Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. To study the potential role of hLF in wound re-epithelialization. The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.

Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture.

PubMed

Furlund, Camilla B; Kristoffersen, Anja B; Devold, Tove G; Vegarud, Gerd E; Jonassen, Christine M

2012-07-01

Many infant formulas are enriched with lactoferrin (Lf) because of its claimed beneficial effects on health. Native bovine Lf (bLf) is known to inhibit in vitro replication of human enteroviruses, a group of pathogenic viruses that replicate in the gut as their primary infection site. On the basis of a model digestion and human gastrointestinal enzymes, we hypothesized that bLf could retain its antiviral properties against enterovirus in the gastrointestinal tract, either as an intact protein or through bioactive peptide fragments released by digestive enzymes. To test our hypothesis, bLf was digested with human gastric juice and duodenal juice in a 2-step in vitro digestion model. Two gastric pH levels and reduction conditions were used to simulate physiological conditions in adults and infants. The antiviral activity of native bLf and of the digested fractions was studied on echovirus 5 in vitro, using various assay conditions, addressing several mechanisms for replication inhibition. Both native and digested bLf fractions revealed a significant inhibitory effect, when added before or simultaneously with the virus onto the cells. Furthermore, a significant stronger sustained antiviral effect was observed when bLf was fully digested in the gastric phase with fast pH reduction to 2.5, compared with native bLf, suggesting the release of antiviral peptides from bLf during the human digestion process. In conclusion, this study demonstrates that bLf may have a role in the prevention of human gastrointestinal virus infection under physiological conditions and that food containing bLf may protect against infection in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

High-frequency measurements of aeolian saltation flux: Field-based methodology and applications

NASA Astrophysics Data System (ADS)

Martin, Raleigh L.; Kok, Jasper F.; Hugenholtz, Chris H.; Barchyn, Thomas E.; Chamecki, Marcelo; Ellis, Jean T.

2018-02-01

Aeolian transport of sand and dust is driven by turbulent winds that fluctuate over a broad range of temporal and spatial scales. However, commonly used aeolian transport models do not explicitly account for such fluctuations, likely contributing to substantial discrepancies between models and measurements. Underlying this problem is the absence of accurate sand flux measurements at the short time scales at which wind speed fluctuates. Here, we draw on extensive field measurements of aeolian saltation to develop a methodology for generating high-frequency (up to 25 Hz) time series of total (vertically-integrated) saltation flux, namely by calibrating high-frequency (HF) particle counts to low-frequency (LF) flux measurements. The methodology follows four steps: (1) fit exponential curves to vertical profiles of saltation flux from LF saltation traps, (2) determine empirical calibration factors through comparison of LF exponential fits to HF number counts over concurrent time intervals, (3) apply these calibration factors to subsamples of the saltation count time series to obtain HF height-specific saltation fluxes, and (4) aggregate the calibrated HF height-specific saltation fluxes into estimates of total saltation fluxes. When coupled to high-frequency measurements of wind velocity, this methodology offers new opportunities for understanding how aeolian saltation dynamics respond to variability in driving winds over time scales from tens of milliseconds to days.

Effect of ceramic membrane channel geometry and uniform transmembrane pressure on limiting flux and serum protein removal during skim milk microfiltration.

PubMed

Adams, Michael C; Hurt, Emily E; Barbano, David M

2015-11-01

Our objectives were to determine the effects of a ceramic microfiltration (MF) membrane's retentate flow channel geometry (round or diamond-shaped) and uniform transmembrane pressure (UTP) on limiting flux (LF) and serum protein (SP) removal during skim milk MF at a temperature of 50°C, a retentate protein concentration of 8.5%, and an average cross-flow velocity of 7 m·s(-1). Performance of membranes with round and diamond flow channels was compared in UTP mode. Performance of the membrane with round flow channels was compared with and without UTP. Using UTP with round flow channel MF membranes increased the LF by 5% when compared with not using UTP, but SP removal was not affected by the use of UTP. Using membranes with round channels instead of diamond-shaped channels in UTP mode increased the LF by 24%. This increase was associated with a 25% increase in Reynolds number and can be explained by lower shear at the vertices of the diamond-shaped channel's surface. The SP removal factor of the diamond channel system was higher than the SP removal factor of the round channel system below the LF. However, the diamond channel system passed more casein into the MF permeate than the round channel system. Because only one batch of each membrane was tested in our study, it was not possible to determine if the differences in protein rejection between channel geometries were due to the membrane design or random manufacturing variation. Despite the lower LF of the diamond channel system, the 47% increase in membrane module surface area of the diamond channel system produced a modular permeate removal rate that was at least 19% higher than the round channel system. Consequently, using diamond channel membranes instead of round channel membranes could reduce some of the costs associated with ceramic MF of skim milk if fewer membrane modules could be used to attain the required membrane area. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in Piglets.

PubMed

Li, Qiuling; Zhao, Jie; Hu, Wenping; Wang, Jianwu; Yu, Tian; Dai, Yunping; Li, Ning

2018-04-03

Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological effects, including antimicrobial and immunomodulatory activities. Recently, it was shown that LF also regulates bone cell activity, suggesting its therapeutic effect on postmenopausal bone loss. However, a minimal amount is known regarding the effects of recombinant human LF (rhLF) supplementation on bone status in young healthy infants. We found osteoblast cell differentiation was significantly promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone status in vivo, we used a piglet model, which is a useful model for human infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation markers, Serum calcium concentration, bone mineral density (BMD), bone mineral content (BMC), tibia bone strength, and the overall metabolite profile analysis showed that rhLF was advantageous to the bone growth in piglets. These findings suggest that rhLF supplementation benefits neonate bone health by modulating bone formation.

Antibacterial effects of lactoferricin B.

PubMed

Vorland, L H; Ulvatne, H; Andersen, J; Haukland, H H; Rekdal, O; Svendsen, J S; Gutteberg, T J

1999-01-01

The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the inhibitory efficacy of lactoferricin of bovine origin (Lf-cin B) on Escherichia coli, Proteus mirabilis and Staphylococcus aureus with or without a cell wall. We found that spheroplasts and protoplasts had a lower MIC than their counterparts with a cell wall. We also compared the efficacies of Lf-cin B (17-31) made of all L-amino acids and all D-amino acids. The peptide made of all D-amino acids was more active than the corresponding L-enantiomer. Furthermore, we examined the influence of Lf-cin B on the motility of E. coli and the influence of temperature on the susceptibility of bacteria exposed to Lf-cin B. Bacteria exposed to sub-MIC of Lf-cin B lost their motility. Bacteria exposed to Lf-cin B at 20 degrees C were more sensitive to Lf-cin B than when exposed at 37 degrees C. These findings indicate that the cell envelope is a limiting step for Lf-cin B to exert its antibiotic effect. We cannot rule out a receptor-mediated first step for Lf-cin B (17-31).

MiR-21 promotes fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis by activating IL-6 expression.

PubMed

Sun, Chao; Tian, Jiwei; Liu, Xinhui; Guan, Guoping

2017-08-26

The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

The lactoferricin B-derived peptide, LfB17-34, induces melanogenesis in B16F10 cells.

PubMed

Huang, Hsiu-Chin; Lin, Hsuan; Huang, Min-Chuan

2017-03-01

Lactoferricin B (LfcinB), a peptide of bovine lactoferrin (LfB), exhibits multiple biological functions, including antimicrobial, antiviral, antioxidant and immunomodulatory activities. However, the role of LfcinB-related peptides in melanogenesis remains unclear. In this study, a set of five LfcinB-related peptides was examined. We found that LfB17‑34, an 18-mer LfcinB-derived peptide, increased melanogenesis in B16F10 melanoma cells without significantly affecting cell viability. LfB17‑34 increased in vitro tyrosinase activity and melanin content in a dose-dependent manner. The results of RT-qPCR and western blot analyses showed that LfB17‑34 increased the mRNA and protein expression of tyrosinase and tyrosinase-related protein 1 (Trp1). Moreover, LfB17‑34 inhibited the phosphorylation of MAPK/Erk, but not p38 and Akt, and constitutively active MEK was able to reverse the LfB17-34-enhanced pigmentation, melanin content, and tyrosinase activity, suggesting a role of Erk signaling in the process of LfB17‑34-mediated pigmentation. Taken together, these results suggest that LfB17‑34 induces melanogenesis in B16F10 cells primarily through increased tyrosinase expression and activity and that LfB17‑34 could be further developed for the treatment of hypopigmentation disorders.

The lactoferricin B-derived peptide, LfB17-34, induces melanogenesis in B16F10 cells

PubMed Central

Huang, Hsiu-Chin; Lin, Hsuan; Huang, Min-Chuan

2017-01-01

Lactoferricin B (LfcinB), a peptide of bovine lactoferrin (LfB), exhibits multiple biological functions, including antimicrobial, antiviral, antioxidant and immuno-modulatory activities. However, the role of LfcinB-related peptides in melanogenesis remains unclear. In this study, a set of five LfcinB-related peptides was examined. We found that LfB17-34, an 18-mer LfcinB-derived peptide, increased melanogenesis in B16F10 melanoma cells without significantly affecting cell viability. LfB17-34 increased in vitro tyrosinase activity and melanin content in a dose-dependent manner. The results of RT-qPCR and western blot analyses showed that LfB17-34 increased the mRNA and protein expression of tyrosinase and tyrosinase-related protein 1 (Trp1). Moreover, LfB17-34 inhibited the phosphorylation of MAPK/Erk, but not p38 and Akt, and constitutively active MEK was able to reverse the LfB17-34-enhanced pigmentation, melanin content, and tyrosinase activity, suggesting a role of Erk signaling in the process of LfB17-34-mediated pigmentation. Taken together, these results suggest that LfB17-34 induces melanogenesis in B16F10 cells primarily through increased tyrosinase expression and activity and that LfB17-34 could be further developed for the treatment of hypopigmentation disorders. PMID:28204812

Antibacterial and cell penetrating effects of LFcin17-30, LFampin265-284, and LF chimera on enteroaggregative Escherichia coli.

PubMed

Reyes-Cortes, Ruth; Acosta-Smith, Erika; Mondragón-Flores, Ricardo; Nazmi, Kamran; Bolscher, Jan G M; Canizalez-Roman, Adrian; Leon-Sicairos, Nidia

2017-02-01

Lactoferrin (LF) is a protein with antimicrobial activity, which is conferred in part by 2 regions contained in its N-terminal lobe. These regions have been used to develop the following synthetic peptides: lactoferricin17-30, lactoferrampin265-284, and LF chimera (a fusion of lactoferricin17-30 and lactoferrampin265-284). We have reported that these LF peptides have antibacterial activity against several pathogenic bacteria; however, the exact mechanism of action has not been established. Here, we report the effects of LF peptides on the viability of enteroaggregative Escherichia coli (EAEC) and the ability of these peptides to penetrate into the bacteria cytoplasm. The viability of EAEC treated with LF peptides was determined via enumeration of colony-forming units, and the binding and internalization of the LF peptides was followed via immunogold labeling and electron microscopy. Treatment of EAEC with 20 and 40 μmol/L LF peptides reduced bacterial growth compared with untreated bacteria. Initially the peptides associated with the plasma membrane, but after 5 to 30 min of incubation, the peptides were found in the cytoplasm. Remarkably, bacteria treated with LF chimera developed cytosolic electron-dense structures that contained the antimicrobial peptide. Our results suggest that the antibacterial mechanism of LF peptides on EAEC involves their interaction with and penetration into the bacteria.

Lassa fever-induced sensorineural hearing loss: A neglected public health and social burden.

PubMed

Mateer, Elizabeth J; Huang, Cheng; Shehu, Nathan Y; Paessler, Slobodan

2018-02-01

Although an association between Lassa fever (LF) and sudden-onset sensorineural hearing loss (SNHL) was confirmed clinically in 1990, the prevalence of LF-induced SNHL in endemic countries is still underestimated. LF, a viral hemorrhagic fever disease caused by Lassa virus (LASV), is endemic in West Africa, causing an estimated 500,000 cases and 5,000 deaths per year. Sudden-onset SNHL, one complication of LF, occurs in approximately one-third of survivors and constitutes a neglected public health and social burden. In the endemic countries, where access to hearing aids is limited, SNHL results in a decline of the quality of life for those affected. In addition, hearing loss costs Nigeria approximately 43 million dollars per year. The epidemiology of LF-induced SNHL has not been characterized well. The complication of LF induced by SNHL is also an important consideration for vaccine development and treatments. However, research into the mechanism has been hindered by the lack of autopsy samples and relevant small animal models. Recently, the first animal model that mimics the symptoms of SNHL associated with LF was developed. Preliminary data from the new animal model as well as the clinical case studies support the mechanism of immune-mediated injury that causes SNHL in LF patients. This article summarizes clinical findings of hearing loss in LF patients highlighting the association between LASV infection and SNHL as well as the potential mechanism(s) for LF-induced SNHL. Further research is necessary to identify the mechanism and the epidemiology of LF-induced SNHL.

Aftereffects of Intense Low-Frequency Sound on Spontaneous Otoacoustic Emissions: Effect of Frequency and Level.

PubMed

Jeanson, Lena; Wiegrebe, Lutz; Gürkov, Robert; Krause, Eike; Drexl, Markus

2017-02-01

The presentation of intense, low-frequency (LF) sound to the human ear can cause very slow, sinusoidal oscillations of cochlear sensitivity after LF sound offset, coined the "Bounce" phenomenon. Changes in level and frequency of spontaneous otoacoustic emissions (SOAEs) are a sensitive measure of the Bounce. Here, we investigated the effect of LF sound level and frequency on the Bounce. Specifically, the level of SOAEs was tracked for minutes before and after a 90-s LF sound exposure. Trials were carried out with several LF sound levels (93 to 108 dB SPL corresponding to 47 to 75 phons at a fixed frequency of 30 Hz) and different LF sound frequencies (30, 60, 120, 240 and 480 Hz at a fixed loudness level of 80 phons). At an LF sound frequency of 30 Hz, a minimal sound level of 102 dB SPL (64 phons) was sufficient to elicit a significant Bounce. In some subjects, however, 93 dB SPL (47 phons), the lowest level used, was sufficient to elicit the Bounce phenomenon and actual thresholds could have been even lower. Measurements with different LF sound frequencies showed a mild reduction of the Bounce phenomenon with increasing LF sound frequency. This indicates that the strength of the Bounce not only is a simple function of the spectral separation between SOAE and LF sound frequency but also depends on absolute LF sound frequency, possibly related to the magnitude of the AC component of the outer hair cell receptor potential.

Species Origin of Genomic Factors in Nicotiana nudicaulis Watson Controlling Hybrid Lethality in Interspecific Hybrids between N. nudicaulis Watson and N. tabacum L

PubMed Central

Liu, Hongshuo; Marubashi, Wataru

2014-01-01

Hybrid lethality is expressed at 28°C in the cross Nicotiana nudicaulis×N. tabacum. The S subgenome of N. tabacum has been identified as controlling this hybrid lethality. To clarify the responsible genomic factor(s) of N. nudicaulis, we crossed N. trigonophylla (paternal progenitor of N. nudicaulis) with N. tabacum, because hybrids between N. sylvestris (maternal progenitor of N. nudicaulis) and N. tabacum are viable when grown in a greenhouse. In the cross N. trigonophylla×N. tabacum, approximately 50% of hybrids were vitrified, 20% were viable, and 20% were nonviable at 28°C. To reveal which subgenome of N. tabacum was responsible for these phenotypes, we crossed N. trigonophylla with two progenitors of N. tabacum, N. sylvestris (SS) and N. tomentosiformis (TT). In the cross N. sylvestris×N. trigonophylla, we confirmed that over half of hybrids of N. sylvestris×N. trigonophylla were vitrified, and none of the hybrids of N. trigonophylla×N. tomentosiformis were. The results imply that the S subgenome, encoding a gene or genes inducing hybrid lethality in the cross between N. nudicaulis and N. tabacum, has one or more genomic factors that induce vitrification. Furthermore, in vitrified hybrids of N. trigonophylla×N. tabacum and N. sylvestris×N. trigonophylla, we found that nuclear fragmentation, which progresses during expression of hybrid lethality, was accompanied by vitrification. This observation suggests that vitrification has a relationship to hybrid lethality. Based on these results, we speculate that when N. nudicaulis was formed approximately 5 million years ago, several causative genomic factors determining phenotypes of hybrid seedlings were inherited from N. trigonophylla. Subsequently, genome downsizing and various recombination-based processes took place. Some of the causative genomic factors were lost and some became genomic factor(s) controlling hybrid lethality in extant N. nudicaulis. PMID:24806486

A protein isolated from human oviductal tissue in vitro secretion, identified as human lactoferrin, interacts with spermatozoa and oocytes and modulates gamete interaction.

PubMed

Zumoffen, C M; Gil, R; Caille, A M; Morente, C; Munuce, M J; Ghersevich, S A

2013-05-01

Is lactoferrin (LF) (detected in oviductal secretion) able to bind to oocytes and sperm and modulate gamete interaction? LF binds to zona pellucida (ZP) and spermatozoa (depending upon the capacitation stage and acrosome status) and inhibits gamete interaction in vitro. Proteins from human oviductal tissue secretion modulate gamete interaction and parameters of sperm function in vitro and some of them bind to sperm, but they remain to be isolated and identified. Proteins were isolated from human oviductal tissue secretion using their sperm membrane binding ability. One of the isolated proteins was identified as human LF and immunolocalized in tubal tissues. LF expression was analyzed in native oviductal fluid and oviduct epithelial cells (at different phases of the menstrual cycle: proliferative, periovulatory and secretory). In addition, the LF binding sites on spermatozoa (at different capacitation and acrosome reaction stages) and on ZP and the dose-dependent effect of LF on gamete interaction were investigated. All experiments were performed at least three times. Tubal tissues obtained from premenopausal patients (scheduled for hysterectomy, n = 23) were cultured in DMEM/Ham's F12 medium and conditioned media (CM) were collected. Motile spermatozoa were obtained by swim-up from normozoospermic semen samples from healthy donors (n = 4). An affinity chromatography with sperm membrane extracts was used to isolate proteins from CM. Isolated proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophresis and further identified by nano liquid chromatography tandem mass spectrometry peptide sequencing. The presence of LF in oviductal tissue was investigated by immunohistochemistry and immunofluorescence and was detected in native oviductal fluid and oviduct epithelial cells homogenates by western blot. LF binding sites on gametes were investigated by incubating gametes with the protein coupled to fluorescein isothiocyanate (FITC). The acrosome reaction was assessed with Pisum sativum agglutinin conjugated with rhodamine. The effect of increasing concentrations of LF (0.1-100 µg/ml) on gamete interaction was evaluated by a sperm-ZP binding assay, using human oocytes donated by women undergoing IVF procedures. A protein isolated by the affinity column was identified as human LF. LF was immunolocalized in human oviductal tissue and detected in oviductal fluid and oviduct epithelial cell homogenates. In the latter case, LF expression was highest at the periovulatory phase of the menstrual cycle (P < 0.01). Different LF binding patterns were observed on spermatozoa depending upon capacitation stage and if the acrosome reaction had occurred. Unstained sperm were most prevalent before capacitation, but after incubation for 6 h under capacitating conditions and in acrosome-reacted sperm LF binding was observed, mainly localized in the equatorial segment and post-acrosomal region of the sperm head. LF binding studies on ZP showed homogenous staining. LF caused a dose-dependent significant inhibition of sperm-ZP interaction, and the effect was already significant (P < 0.01) with the lowest LF concentration used. This study has investigated the effect of LF only on human gamete interaction in vitro and thus has some limitations. Further investigations of the potential mechanisms involved in LF action both on gamete function in vitro and in vivo in animal models are needed to confirm the role of this protein in the reproductive process. The present data indicate that human oviductal LF expression is cycle dependent and inhibited gamete interaction in vitro. No previous data were available about potential direct effects of LF on gamete interaction. It could be thought that the protein is involved in the regulation of the reproductive process, perhaps contributing to prevent polyspermy. Thus, further research is needed to clarify the potential role of LF in the regulation of the fertilization process. This study was supported by grants from FONCYT (PICT 01095, S.A.G., M.J.M) and SECyT UNR (PIDBIO238, S.A.G). The authors have no conflict of interest to declare.

The ALHAMBRA survey: B-band luminosity function of quiescent and star-forming galaxies at 0.2 ≤ z < 1 by PDF analysis

NASA Astrophysics Data System (ADS)

López-Sanjuan, C.; Tempel, E.; Benítez, N.; Molino, A.; Viironen, K.; Díaz-García, L. A.; Fernández-Soto, A.; Santos, W. A.; Varela, J.; Cenarro, A. J.; Moles, M.; Arnalte-Mur, P.; Ascaso, B.; Montero-Dorta, A. D.; Pović, M.; Martínez, V. J.; Nieves-Seoane, L.; Stefanon, M.; Hurtado-Gil, Ll.; Márquez, I.; Perea, J.; Aguerri, J. A. L.; Alfaro, E.; Aparicio-Villegas, T.; Broadhurst, T.; Cabrera-Caño, J.; Castander, F. J.; Cepa, J.; Cerviño, M.; Cristóbal-Hornillos, D.; González Delgado, R. M.; Husillos, C.; Infante, L.; Masegosa, J.; del Olmo, A.; Prada, F.; Quintana, J. M.

2017-03-01

Aims: Our goal is to study the evolution of the B-band luminosity function (LF) since z 1 using ALHAMBRA data. Methods: We used the photometric redshift and the I-band selection magnitude probability distribution functions (PDFs) of those ALHAMBRA galaxies with I ≤ 24 mag to compute the posterior LF. We statistically studied quiescent and star-forming galaxies using the template information encoded in the PDFs. The LF covariance matrix in redshift - magnitude - galaxy type space was computed, including the cosmic variance. That was estimated from the intrinsic dispersion of the LF measurements in the 48 ALHAMBRA sub-fields. The uncertainty due to the photometric redshift prior is also included in our analysis. Results: We modelled the LF with a redshift-dependent Schechter function affected by the same selection effects than the data. The measured ALHAMBRA LF at 0.2 ≤ z< 1 and the evolving Schechter parameters both for quiescent and star-forming galaxies agree with previous results in the literature. The estimated redshift evolution of MB* ∝ Qz is QSF = -1.03 ± 0.08 and QQ = -0.80 ± 0.08, and of log 10φ∗ ∝ Pz is PSF = -0.01 ± 0.03 and PQ = -0.41 ± 0.05. The measured faint-end slopes are αSF = -1.29 ± 0.02 and αQ = -0.53 ± 0.04. We find a significant population of faint quiescent galaxies with MB ≳ -18, modelled by a second Schechter function with slope β = -1.31 ± 0.11. Conclusions: We present a robust methodology to compute LFs using multi-filter photometric data. The application to ALHAMBRA shows a factor 2.55 ± 0.14 decrease in the luminosity density jB of star-forming galaxies, and a factor 1.25 ± 0.16 increase in the jB of quiescent ones since z = 1, confirming the continuous build-up of the quiescent population with cosmic time. The contribution of the faint quiescent population to jB increases from 3% at z = 1 to 6% at z = 0. The developed methodology will be applied to future multi-filter surveys such as J-PAS. Based on observations collected at the German-Spanish Astronomical Center, Calar Alto (CAHA), jointly operated by the Max-Planck-Institut für Astronomie (MPIA) at Heidelberg and the Instituto de Astrofísica de Andalucía (CSIC)

Lactoferrin and necrotizing enterocolitis.

PubMed

Sherman, Michael P

2013-03-01

Lactoferrin (LF) is a multifunctional protein and a member of the transferrin family. LF and lysozyme in breast milk kill bacteria. In the stomach, pepsin digests and releases a potent peptide antibiotic called lactoferricin from native LF. The antimicrobial characteristics of LF may facilitate a healthy intestinal microbiome. LF is the major whey in human milk; its highest concentration is in colostrum. This fact highlights early feeding of colostrum and also fresh mature milk as a way to prevent necrotizing enterocolitis. Copyright © 2013 Elsevier Inc. All rights reserved.

Safety and efficacy of lactoferrin versus ferrous sulphate in curing iron deficiency and iron deficiency anaemia in hereditary thrombophilia pregnant women: an interventional study.

PubMed

Paesano, Rosalba; Pacifici, Enrica; Benedetti, Samanta; Berlutti, Francesca; Frioni, Alessandra; Polimeni, Antonella; Valenti, Piera

2014-10-01

Objective Evaluate the safety and efficacy of bovine lactoferrin (bLf) versus the ferrous sulphate standard intervention in curing iron deficiency (ID) and ID anaemia (IDA) in pregnant women affected by hereditary thrombophilia (HT). Design Interventional study. Setting Secondary-level hospital for complicated pregnancies in Rome, Italy. Population 295 HT pregnant women (≥18 years) suffering from ID/IDA. Methods Women were enrolled in Arm A or B in accordance with their personal choice. In Arm A, 156 women received oral administration of 100 mg of bLf twice a day; in Arm B, 139 women received 520 mg of ferrous sulphate once a day. Therapies lasted until delivery. Main outcome measures Red blood cells, haemoglobin, total serum iron, serum ferritin (haematological parameters) were assayed before and every 30 days during therapy until delivery. Serum IL-6, key factor in inflammatory and iron homeostasis disorders, was detected at enrolment and after therapy at delivery. Possible maternal, foetal, and neonatal adverse effects were assessed. Results Haematological parameters were significantly higher in Arm A than in Arm B pregnant women (P ≤ 0.0001). Serum IL-6 significantly decreased in bLf-treated women and increased in ferrous sulphate-treated women. BLf did not exert any adverse effect. Adverse effects in 16.5 % of ferrous sulphate-treated women were recorded. Arm A women experienced no miscarriage compared to five miscarriages in Arm B women. Conclusions Differently from ferrous sulphate, bLf is safe and effective in curing ID/IDA associated with a consistent decrease of serum IL-6. The absence of miscarriage among bLf-treated women provided an unexpected benefit. ClinicalTrials.gov Identifier NCT01221844.

High N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated with Reduced Heart Rate Variability in Acute Myocardial Infarction

PubMed Central

Lorgis, Luc; Moreau, Daniel; Mock, Laurent; Daumas, Bernadette; Potard, Daniel; Touzery, Claude; Cottin, Yves; Zeller, Marianne

2012-01-01

Aim We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV) and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP) in patients with acute myocardial infarction (MI). Methods and Results The mean of standard deviation of RR intervals (SDNN), the percentage of RR intervals with >50 ms variation (pNN50), square root of mean squared differences of successive RR intervals (rMSSD), and frequency domain parameters (total power (TP), high frequency and low frequency power ratio (LF/HF)) were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche) was measured from blood samples taken on admission. The median (IQR) Nt-proBNP level was 681(159–2432) pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = −0.19, p<0.001), LF/HF (r = −0.37, p<0.001), and LF (r = −0.29, p<0.001) but not HF (r = −0.043, p = 0.172). Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE) = −0.065(0.015), p<0.001)), even after adjustment for confounders. Conclusions In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI. PMID:23071500

Changes in heart rate variability in first-episode drug-naïve adolescents with major depressive disorder: A 12-week prospective study.

PubMed

Park, Sang-Won; Lee, Jong-Ha; Kim, Jihyun; Suh, Sangil; Lee, Moon-Soo

2018-06-02

Major depressive disorder (MDD) is a common mental disorder, the onset of which frequently occurs during adolescence. While differences in heart rate variability (HRV) between depressed and healthy participants have previously been observed, results have been inconsistent. This study thus investigated the features of HRV in adolescents with MDD. We recruited first-episode drug-naïve adolescents aged 13-18 years who had been diagnosed with MDD, and healthy age-matched controls. HRV was measured before and after a 12-week antidepressant treatment. We compared HRV measures between patient group and control group. We also tried to find correlation between HRV measures and depression rating scales. Fifty-seven participants were included (patient group: n = 31; control group: n = 26). The patient group showed a lower normalized high frequency (HF norm), a higher normalized low frequency (LF norm), and a higher LF/HF ratio than did the control group. After treatment, LF was significantly decreased within the patient group compared to baseline. Hamilton Depression Rating Scales and Children's Depression Inventory scores were positively correlated with LF norm and LF/HF ratio, and negatively correlated with HF norm, when included all participants in analysis LIMITATIONS: Sample size of this study was small to assess influences of confounding factors on HRV. And follow up period was relatively short to see impact of pharmacotherapy. An imbalance of the autonomic nervous system might be a meaningful feature of adolescent MDD, and HRV might represent a potential biological marker for pathophysiological changes in MDD. Copyright © 2018 Elsevier B.V. All rights reserved.

Fertilizer performance of liquid fraction of digestate as synthetic nitrogen substitute in silage maize cultivation for three consecutive years.

PubMed

Sigurnjak, I; Vaneeckhaute, C; Michels, E; Ryckaert, B; Ghekiere, G; Tack, F M G; Meers, E

2017-12-01

Following changes over recent years in fertilizer legislative framework throughout Europe, phosphorus (P) is taking over the role of being the limiting factor in fertilizer application rate of animal manure. This results in less placement area for spreading animal manure. As a consequence, more expensive and energy demanding synthetic fertilizers are required to meet crop nutrient requirements despite existing manure surpluses. Anaerobic digestion followed by mechanical separation of raw digestate, results in liquid fraction (LF) of digestate, a product poor in P but rich in nitrogen (N) and potassium (K). A 3-year field experiment was conducted to evaluate the impact of using the LF of digestate as a (partial) substitute for synthetic N fertilizer. Two different fertilization strategies, the LF of digestate in combination with respectively animal manure and digestate, were compared to the conventional fertilization regime of raw animal manure with synthetic fertilizers. Results from the 3-year trial indicate that the LF of digestate may substitute synthetic N fertilizers without crop yield losses. Through fertilizer use efficiency assessment it was observed that under-fertilization of soils with a high P status could reduce P availability and consequently the potential for P leaching. Under conditions of lower K application, more sodium was taken up by the crop. In arid regions, this effect might reduce the potential risk of salt accumulation that is associated with organic fertilizer application. Finally, economic and ecological benefits were found to be higher when LF of digestate was used as a synthetic N substitute. Future perspectives indicate that nutrient variability in bio-based fertilizers will be one of the greatest challenges to address in the future utilization of these products. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting delivery of etoposide to inhibit the growth of human glioblastoma multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide) nanoparticles.

PubMed

Kuo, Yung-Chih; Chen, Yu-Chun

2015-02-01

Lactoferrin (Lf) and folic acid (FA) were crosslinked on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for transporting etoposide across the blood-brain barrier (BBB) and treating human brain malignant glioblastoma. Lf- and FA-grafted PLGA NPs (Lf/FA/PLGA NPs) were employed to permeate the monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and to inhibit the multiplication of U87MG cells. Lf/FA/PLGA NPs showed a satisfactory entrapment efficiency of etoposide and characteristics of sustained drug release. When compared with PLGA NPs, the permeability coefficient for etoposide across the BBB using Lf/FA/PLGA NPs increased about twofold. The antiproliferative efficacy against the growth of U87MG cells was in the following order: Lf/FA/PLGA NPs>FA/PLGA NPs>PLGA NPs>free etoposide solution. In addition, the targeting ability of Lf/FA/PLGA NPs was evidenced by immunostaining of Lf receptor on HBMECs and folate receptor on U87MG cells during endocytosis. Lf/FA/PLGA NPs with loaded etoposide can be a promising anticancer pharmacotherapy to enhance the delivery of etoposide to malignant brain tumors for preclinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

PubMed Central

Wei, Minyan; Guo, Xiucai; Tu, Liuxiao; Zou, Qi; Li, Qi; Tang, Chenyi; Chen, Bao; Xu, Yuehong; Wu, Chuanbin

2015-01-01

Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma (HCC) cells because of its specific binding with asialoglycoprotein receptor (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified, polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded Lf-PLS system had spherical or oval vesicles, with mean particle size approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive cells (P<0.05) but not in ASGPR-negative cells (P>0.05). Cytotoxicity assay by MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf modification (P<0.05). The in vivo antitumor studies on male BALB/c nude mice bearing HepG2 xenografts demonstrated that DOX-loaded Lf-PLS had significantly stronger antitumor efficacy compared with PLS (P<0.05) and free DOX (P<0.05). All these results demonstrated that a DOX-loaded Lf-PLS might have great potential application for HCC-targeting therapy. PMID:26316745

Effects of irrigation water salinity on evapotranspiration modified by leaching fractions in hot pepper plants.

PubMed

Qiu, Rangjian; Liu, Chunwei; Wang, Zhenchang; Yang, Zaiqiang; Jing, Yuanshu

2017-08-03

We investigated whether leaching fraction (LF) is able to modify the effects of irrigation water salinity (EC iw ) on evapotranspiration (ET). We conducted an experiment with a completely randomized block design using five levels of EC iw and two LFs. Results showed that the electrical conductivity of drainage water (EC dw ) in an LF of 0.29 was considerably higher during the 21-36 days after transplanting (DAT), and considerably lower after 50 DAT than in an LF of 0.17. The hourly, nighttime, daily, cumulative and seasonal ET all decreased considerably as a result of an increase in the EC iw . The daily ET started to be considerably higher in the LF of 0.29 than in the LF of 0.17 from 65 DAT. Compared with the LF of 0.17, the seasonal ET in the LF of 0.29 under various EC iw levels increased by 4.8%-8.7%. The Maas and Hoffman and van Genuchten and Hoffman models both corresponded well with the measured relative seasonal ET and the LF had no marked effects on these model parameters. Collectively, an increase in the level of EC iw always decreased the ET substantially. An increase in the LF increased the ET considerably, but there was a time lag.

Rapid identification of Lonicerae japonicae Flos and Lonicerae Flos by Fourier transform infrared (FT-IR) spectroscopy and two-dimensional correlation analysis

NASA Astrophysics Data System (ADS)

Yan, Rui; Chen, Jian-bo; Sun, Su-qin; Guo, Bao-lin

2016-11-01

Lonicerae japonicae Flos (LJF) and Lonicerae Flos (LF) are widely-used herbs derived from several plants of the genus Lonicera with similar appearances. LF are usually misused or counterfeited as LJF for economically motivated adulteration. However, the saponins in LF may cause serious side-effects. In this research, the infrared spectroscopic tri-step identification approach is used to develop a simple and rapid method to discriminate LJF and LF to ensure the safety and efficacy of these herbal drugs. In the primary identification by Fourier transform infrared spectra, LJF and LF show different peaks near 1534, 1404, and 781 cm-1. In the secondary identification by the second derivative infrared spectra, LJF and LF show more different peaks near 1078, 1050, 988, 923, 855, 815, and 781 cm-1. In the tertiary identification by the two-dimensional correlation infrared spectra, the differences between LJF and LF are shown more remarkably and convincingly. The results show the potential of the infrared spectroscopic tri-step identification approach in the rapid identification of LJF and LF when the samples are too few to build a statistical recognition rule. This should be very helpful to ensure the quality, safety, and efficacy of LJF and LF for clinical applications.

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells.

PubMed

Ying, Xiaozhou; Cheng, Shaowen; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Shen, Yue; Cheng, Xiaojie; Peng, Lei; Zi Xu, Hua; Zhu Lu, Chuan

2012-03-01

Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells. The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 μg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR). Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 μg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment. We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

Serum disposition of bovine lactoferrin after oral and anal administration and its proteolytic cleavage by gastric transit in rainbow trout (Oncorhynchus mykiss W.).

PubMed

Cecchini, Stefano; Caputo, Anna R

2009-01-01

Several studies have shown an immunomodulatory effect of orally administered bovine lactoferrin (LF) in fish, but the process of digestion was not characterized. In the present study, we investigated the fate of bovine LF after oral and anal administration, and studied the appearance of intact LF in the bloodstream and its proteolytic attack during the gastric transit in rainbow trout (Oncorhynchus mykiss) held at 9 degrees C and 18 degrees C. Data obtained showed the presence of intact bovine LF in the bloodstream only after anal administration in fish held at 18 degrees C and the presence of several peptides derived from bovine LF in the gastric content. Immunoblotting analysis showed that only a part of bovine LF-derived peptides reacted with the applied anti-bovine LF antibody. The concentration of intact bovine LF, after 30 min of administration, in the gastric content of fish reared at 18 degrees C, being extremely low, if any, led us to suspect that the immunoregulatory effect of dietary bovine LF shown in fish by several authors is not due to the intact form but to bioactive fragments, originated by the proteolytic attack during the gastric transit, as demonstrated in higher vertebrates.

Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin

PubMed Central

Hayworth, J L; Kasper, K J; Leon-Ponte, M; Herfst, C A; Yue, D; Brintnell, W C; Mazzuca, D M; Heinrichs, D E; Cairns, E; Madrenas, J; Hoskin, D W; McCormick, J K; Haeryfar, S M M

2009-01-01

Staphylococcal enterotoxin B (SEB) is a pyrogenic exotoxin and a potent superantigen which causes massive T cell activation and cytokine secretion, leading to profound immunosuppression and morbidity. The inhibition of SEB-induced responses is thus considered a goal in the management of certain types of staphylococcal infections. Lactoferrin (LF) is a multi-functional glycoprotein with both bacteriostatic and bactericidal activities. In addition, LF is known to have potent immunomodulatory properties. Given the anti-microbial and anti-inflammatory properties of this protein, we hypothesized that LF can modulate T cell responses to SEB. Here, we report that bovine LF (bLF) was indeed able to attenuate SEB-induced proliferation, interleukin-2 production and CD25 expression by human leucocyte antigen (HLA)-DR4 transgenic mouse T cells. This inhibition was not due to bLF's iron-binding capacity, and could be mimicked by the bLF-derived peptide lactoferricin. Cytokine secretion by an engineered SEB-responsive human Jurkat T cell line and by peripheral blood mononuclear cells from healthy donors was also inhibited by bLF. These findings reveal a previously unrecognized property of LF in modulation of SEB-triggered immune activation and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome. PMID:19659771

[Isolation and purification of recombinant human lactoferrin (rhLF) from transgenic rice and its antibacterial activities].

PubMed

Wu, Jinghuan; Yang, Lichen; Liu, Gaige; Gong, Zhaolong; Liu, Jikai; Hu, Yujie; Guo, Yunchang; Piao, Jianhua; Shen, Zhicheng; Yang, Xiaoguang

2013-05-01

To study the isolation and purification of recombinant human lactoferrin (rhLF) from transgenic rice, and to check its antibacterial activities. After isolated rhLF from transgenic rice via saturated ammonium sulfate precipitation, then purified it through CM Sepharose FF-exchange chromatography and molecular sieve chromatography Sephadex G25. The inhibition effects under different concentrations of rhLF (0.25, 0.5, 1.0, 2.0, 4.0, and 5.0 mg/ml) against Salmonella typhimurium, Staphyloccocus aureus, Bacillus cereus, Listeria monocytogenes were observed, using broth microdilution method. The rhLF was obtained at a higher purity (about 90%) through successful isolation and purification. After Coomassie blue staining, Westernblot and mass spectrometer analysis, it was identified as the purpose protein with the molecular weight of approximately 79 kDa. The antibacterial experiments showed that 5 mg/ml and 4 mg/ml rhLF could inhibite Salmonella typhimurium and Staphylococcus aureus persistently, 2 mg/ml and 1 mg/ml rhLF showed a significant inhibitory effects in the later period; while 0.5 mg/ml or lower concentration, showed no inhibitory effects. As to Bacillus cereus, only 5 mg/ml and 4 mg/ml rhLF exhibited certain inhibitory effects within 18 hours. Listeria monocytogenes was inhibited within 18 hours just at 5 mg/ml rhLF. The rhLF could be successfully separated and purified from transgenic rice, and the purified protein still has significant antibacterial activities.

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations.

PubMed

Hilz, Max J; Wang, Ruihao; Marthol, Harald; Liu, Mao; Tillmann, Alexandra; Riss, Stephan; Hauck, Paulina; Hösl, Katharina M; Wasmeier, Gerald; Stemper, Brigitte; Köhrmann, Martin

2016-06-15

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03-0.15Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade. In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0°C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF-CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p<0.05). Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA. Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation. Copyright © 2016 Elsevier B.V. All rights reserved.

Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways.

PubMed

Jiang, Rulan; Lönnerdal, Bo

2017-02-01

Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

Lactobacillus fermentum ZYL0401 Attenuates Lipopolysaccharide-Induced Hepatic TNF-α Expression and Liver Injury via an IL-10- and PGE2-EP4-Dependent Mechanism

PubMed Central

Lv, Longxian; Yang, Jianzhuan; Lu, Haifeng; Li, Lanjuan

2015-01-01

Lipopolysaccharide (LPS) has essential role in the pathogenesis of D-galactosamine-sensitized animal models and alcoholic liver diseases of humans, by stimulating release of pro-inflammatory mediators that cause hepatic damage and intestinal barrier impairment. Oral pretreatment of probiotics has been shown to attenuate LPS-induced hepatic injury, but it is unclear whether the effect is direct or due to improvement in the intestinal barrier. The present study tested the hypothesis that pretreatment with probiotics enables the liver to withstand directly LPS-induced hepatic injury and inflammation. In a mouse model of LPS-induced hepatic injury, the levels of hepatic tumor necrosis factor-alpha (TNF-α) and serum alanine aminotransferase (ALT) of mice with depleted intestinal commensal bacteria were not significantly different from that of the control models. Pre-feeding mice for 10 days with Lactobacillus fermentum ZYL0401 (LF41), significantly alleviated LPS-induced hepatic TNF-α expression and liver damage. After LF41 pretreatment, mice had dramatically more L.fermentum-specific DNA in the ileum, significantly higher levels of ileal cyclooxygenase (COX)-2 and interleukin 10 (IL-10) and hepatic prostaglandin E2 (PGE2). However, hepatic COX-1, COX-2, and IL-10 protein levels were not changed after the pretreatment. There were also higher hepatic IL-10 protein levels after LPS challenge in LF41-pretreaed mice than in the control mice. Attenuation of hepatic TNF-α was mediated via the PGE2/E prostanoid 4 (EP4) pathway, and serum ALT levels were attenuated in an IL-10-dependent manner. A COX-2 blockade abolished the increase in hepatic PGE2 and IL-10 associated with LF41. In LF41-pretreated mice, a blockade of IL-10 caused COX-2-dependent promotion of hepatic PGE2, without affecting hepatic COX-2levels. In LF41-pretreated mice, COX2 prevented enhancing TNF-α expression in both hepatic mononuclear cells and the ileum, and averted TNF-α-mediated increase in intestinal permeability. Together, we demonstrated that LF41 pre-feeding enabled the liver to alleviate LPS-induced hepatic TNF-α expression and injury via a PGE2-EP4- and IL-10-dependent mechanism. PMID:25978374

Lassa fever in post-conflict sierra leone.

PubMed

Shaffer, Jeffrey G; Grant, Donald S; Schieffelin, John S; Boisen, Matt L; Goba, Augustine; Hartnett, Jessica N; Levy, Danielle C; Yenni, Rachael E; Moses, Lina M; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J; Jones, Abigail B; Illick, Megan M; Kulakosky, Peter C; Haislip, Allyson M; Bishop, Christopher M; Elliot, Deborah H; Brown, Bethany L; Zhu, Hu; Hastie, Kathryn M; Andersen, Kristian G; Gire, Stephen K; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B; Spence, Jennifer S; Cross, Robert W; Geisbert, Joan B; Folarin, Onikepe A; Happi, Christian T; Pitts, Kelly R; Geske, F Jon; Geisbert, Thomas W; Saphire, Erica Ollmann; Robinson, James E; Wilson, Russell B; Sabeti, Pardis C; Henderson, Lee A; Khan, S Humarr; Bausch, Daniel G; Branco, Luis M; Garry, Robert F

2014-03-01

Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles.

PubMed

Garg, Anuj; Bhalala, Kripal; Tomar, Devendra Singh; Wahajuddin

2017-01-10

The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were prepared using binary lipid mixture of stearic acid and caprylic acid stabilized with TPGS (D-alpha tocopheryl polyethylene glycol 1000 succinate) and Poloxamer 188. Developed LF-SLNs were characterized for particle size distribution, zeta potential, entrapment efficiency, solid state properties and biopharmaceutical properties including in situ intestinal permeability and oral bioavailability. The particle size distribution, zeta potential and entrapment efficiency of optimized batch (LF-SLN7) was found to be 357.7±43.27nm, 25.29±1.15mV and 97.35±0.30%, respectively. DSC thermographs showed loss of crystalline nature of lumefantrine in LF-SLNs. In situ single pass intestinal permeability study (SPIP) study indicated significant enhancement in the effective intestinal permeability of LF from LF-SLN7 as compared to that of control. Pharmacokinetic study also showed significant increase in Cmax and area under curve (AUC0- ∞ ) from LF-SLN7 (3860±521ng/mL and 43181±2557h×ng/mL, respectively) as compared to that of LF-control suspension (1425±563ng/mL and 19586±1537h×ng/mL, respectively). Thus, developed LF-SLNs can be promising to overcome P-gp efflux pump and enhance the oral bioavailability of lumefantrine. Copyright © 2016 Elsevier B.V. All rights reserved.

Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

PubMed Central

Adam, Clare L.; Thomson, Lynn M.; Williams, Patricia A.; Ross, Alexander W.

2015-01-01

Consumption of a high fat diet promotes obesity and poor metabolic health, both of which may be improved by decreasing caloric intake. Satiety-inducing ingredients such as dietary fibre may be beneficial and this study investigates in diet-induced obese (DIO) rats the effects of high or low fat diet with or without soluble fermentable fibre (pectin). In two independently replicated experiments, young adult male DIO rats that had been reared on high fat diet (HF; 45% energy from fat) were given HF, low fat diet (LF; 10% energy from fat), HF with 10% w/w pectin (HF+P), or LF with 10% w/w pectin (LF+P) ad libitum for 4 weeks (n = 8/group/experiment). Food intake, body weight, body composition (by magnetic resonance imaging), plasma hormones, and plasma and liver lipid concentrations were measured. Caloric intake and body weight gain were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Body fat mass increased in HF, was maintained in LF, but decreased significantly in LF+P and HF+P groups. Final plasma leptin, insulin, total cholesterol and triglycerides were lower, and plasma satiety hormone PYY concentrations were higher, in LF+P and HF+P than in LF and HF groups, respectively. Total fat and triglyceride concentrations in liver were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Therefore, the inclusion of soluble fibre in a high fat (or low fat) diet promoted increased satiety and decreased caloric intake, weight gain, adiposity, lipidaemia, leptinaemia and insulinaemia. These data support the potential of fermentable dietary fibre for weight loss and improving metabolic health in obesity. PMID:26447990

Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11

PubMed Central

Morici, Paola; Fais, Roberta; Rizzato, Cosmeri

2016-01-01

The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans. PMID:27902776

Resolving Ambiguities in the LF/HF Ratio: LF-HF Scatter Plots for the Categorization of Mental and Physical Stress from HRV.

PubMed

von Rosenberg, Wilhelm; Chanwimalueang, Theerasak; Adjei, Tricia; Jaffer, Usman; Goverdovsky, Valentin; Mandic, Danilo P

2017-01-01

It is generally accepted that the activities of the autonomic nervous system (ANS), which consists of the sympathetic (SNS) and parasympathetic nervous systems (PNS), are reflected in the low- (LF) and high-frequency (HF) bands in heart rate variability (HRV)-while, not without some controversy, the ratio of the powers in those frequency bands, the so called LF-HF ratio (LF/HF), has been used to quantify the degree of sympathovagal balance. Indeed, recent studies demonstrate that, in general: (i) sympathovagal balance cannot be accurately measured via the ratio of the LF- and HF- power bands; and (ii) the correspondence between the LF/HF ratio and the psychological and physiological state of a person is not unique. Since the standard LF/HF ratio provides only a single degree of freedom for the analysis of this 2D phenomenon, we propose a joint treatment of the LF and HF powers in HRV within a two-dimensional representation framework, thus providing the required degrees of freedom. By virtue of the proposed 2D representation, the restrictive assumption of the linear dependence between the activity of the autonomic nervous system (ANS) and the LF-HF frequency band powers is demonstrated to become unnecessary. The proposed analysis framework also opens up completely new possibilities for a more comprehensive and rigorous examination of HRV in relation to physical and mental states of an individual, and makes possible the categorization of different stress states based on HRV. In addition, based on instantaneous amplitudes of Hilbert-transformed LF- and HF-bands, a novel approach to estimate the markers of stress in HRV is proposed and is shown to improve the robustness to artifacts and irregularities, critical issues in real-world recordings. The proposed approach for resolving the ambiguities in the standard LF/HF-ratio analyses is verified over a number of real-world stress-invoking scenarios.

Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11.

PubMed

Morici, Paola; Fais, Roberta; Rizzato, Cosmeri; Tavanti, Arianna; Lupetti, Antonella

2016-01-01

The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans.

Lactoferrin inhibits dexamethasone-induced chondrocyte impairment from osteoarthritic cartilage through up-regulation of extracellular signal-regulated kinase 1/2 and suppression of FASL, FAS, and Caspase 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tu, Yihui; Xue, Huaming; Institute of Life Science, College of Medicine, Swansea University, Singleton Park

Highlights: •Dex exerts dose-dependant inhibition of HACs viability and induction of apoptosis. •Dex-induced impairment of chondrocytes was attenuated by rhLF. •ERK and FASL/FAS signaling are involved in the effects of rhLF. •OA patients with glucocorticoid-induced cartilage damage may benefit from treatment with rhLF. -- Abstract: Dexamethasone (Dex) is commonly used for osteoarthritis (OA) with excellent anti-inflammatory and analgesic effect. However, Dex also has many side effects following repeated use over prolonged periods mainly through increasing apoptosis and inhibiting proliferation. Lactoferrin (LF) exerts significantly anabolic effect on many cells and little is known about its effect on OA chondrocytes. Therefore, themore » aim of this study is to investigate whether LF can inhibit Dex-induced OA chondrocytes apoptosis and explore its possible molecular mechanism involved in. MTT assay was used to determine the optimal concentration of Dex and recombinant human LF (rhLF) on chondrocytes at different time and dose points. Chondrocytes were then stimulated with Dex in the absence or presence of optimal concentration of rhLF. Cell proliferation and viability were evaluated using MTT and LIVE/DEAD assay, respectively. Cell apoptosis was evaluated by multi-parameter apoptosis assay kit using both confocal microscopy and flow cytometry, respectively. The expression of extracellular signal-regulated kinase (ERK), FAS, FASL, and Caspase-3 (CASP3) at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The optimal concentration of Dex (25 μg/ml) and rhLF (200 μg/ml) were chosen for the following experiments. rhLF significantly reversed the detrimental effect of Dex on chondrocytes proliferation, viability, and apoptosis. In addition, rhLF significantly prevented Dex-induced down-regulation of ERK and up-regulation of FAS, FASL, and CASP3. These findings demonstrated that rhLF acts as an anabolic effect on chondrocytes through significantly reversing Dex-induced chondrocytes apoptosis. This study may contribute to further investigating the clinical application of LF on OA.« less

[WHO programs "Acute Myocardial Infarction Register", MONICA: thirty years (1977-2006) of epidemiological studies of myocardial infarction in a high-risk population].

PubMed

Gafarov, V V; Gafarova, A V

2011-01-01

To reveal 30 year (1977-2006) trends of myocardial infarction (MI) morbidity, lethality and mortality in population of the West Siberia megapolis (Novosibirsk). WHO programs "Acute Myocardial Infarction Register (AMIR) and MONICA covered 3 districts of Novosibirsk. MI morbidity in 25-64 year old population of Novosibirsk (high-risk population) in Russia is one of the highest in the world. MI morbidity was stable for 30 years excluding in 1988, 1994 and 1998 when it rose and in 2002-2004, 2006 when it lowered. Changes in mortality and lethality resemble changes in morbidity trend excluding 1977-1978 (fall) and 2002-2005 (rise). Prehospital mortality and lethality were much higher than those in hospital. Mortality and lethality in 1988, 1994, 1998 and 2002-2005 increased due to prehospital lethality and mortality, while it decreased in 1977-1978 due to hospital one. Reduction of mortality and lethality in stable MI morbidity shows improvement of medical care for MI patients, increased lethality and mortality in MI morbidity decline reflect deterioration of such care. Changes in behavioral and somatic factors of cardiovascular risk in population of Novosibirsk for 30 years were not observed while psychosocial risk factors gain a significant importance. By indirect indications, MI morbidity, mortality and lethality mark growing social stress in the population. MI mortality is 2-3 times higher than that of alcohol and is a basic factor of mortality increase in the population of Russia. MI morbidity, mortality and lethality are markers of social stress in population.

[The role of lactoferrin in the proper development of newborns].

PubMed

Artym, Jolanta; Zimecki, Michał

2005-01-01

Colostrum and milk contain, in addition to nutritional constituents, also proteins crucial for the normal development of the offspring. Lactoferrin (LF) belongs to the family of iron-binding proteins and exhibits a wide spectrum of antimicrobial and immunotropic properties. LF is particularly resistant to proteolytic degradation in alimentary tract, in contrast to other milk proteins, e.g. casein. In any case, LF-derived peptides also possess potent antibacterial activities. LF is absorbed from the intestine by means of specific receptors located on brush border cells. Administered orally, LF stimulates both local and systemic immune response. LF plays a role in the absorption of nutrients. The protein can deliver such metal ions as iron, manganese, and zinc and facilitate the absorption of sugars. LF stimulates the proliferation of gut endothelial cells and the growth of gut-associated lymphatic follicles. This property suggests the possibility of applying LF in premature infants and patients with damaged intestinal mucus. LF controls the proper composition of the gut microflora. It suppresses the growth of pathogenic bacteria while promoting the multiplication of nonpathogenic Lactobacillus and Bifidobacterium. Newborns fed an artificial diet develop harmful microflora (Enterococcus, Enterobacter, Bacteroides, Escherichia). The non-pathogenic microflora ensures low pH, produces some vitamins, increases the activity of NK cells, T lymphocytes, and macrophages, promotes the production of protective immunoglobulins, and lowers the risk of allergies. In studies on mice, LF was found to be protective in bacteremia and endotoxemia. The protein stimulates the activity of reticulo-endothelial system cells and elicits myelopoiesis, thus increasing the killing and clearance of bacteria. In the model of experimental endotoxemia, LF inhibits the activity of pro-inflammatory cytokines, nitric oxide, and reactive forms of oxygen. LF can also promote the differentiation of T and B cells from their immature precursors and increases the activity of NK and LAK cells. It also protects against the toxicity of reactive oxygen radicals. This property may be particularly relevant when baby food, based on modified cow's milk, contains mineral iron, which may be a source of harmful free radicals. In summary, it is obvious that natural human milk has the best value for newborns. Supplementation of artificial baby food with LF seems essential to improve the protective and immunoenhancing property of this kind of diet. It is clear that cow's milk is not appropriate for human newborns. Cow's milk contains 50 times less LF, only traces of lysozyme, and lower concentrations of other whey proteins and immunologically relevant immunoglobulins. Therefore commercially available baby foods (United States, Japan) are supplemented with LF.

Association between heart rhythm and cortical sound processing.

PubMed

Marcomini, Renata S; Frizzo, Ana Claúdia F; de Góes, Viviane B; Regaçone, Simone F; Garner, David M; Raimundo, Rodrigo D; Oliveira, Fernando R; Valenti, Vitor E

2018-04-26

Sound signal processing signifies an important factor for human conscious communication and it may be assessed through cortical auditory evoked potentials (CAEP). Heart rate variability (HRV) provides information about heart rate autonomic regulation. We investigated the association between resting HRV and CAEP. We evaluated resting HRV in the time and frequency domain and the CAEP components. The subjects remained at rest for 10 minutes for HRV recording, then they performed the CAEP examinations through frequency and duration protocols in both ears. Linear regression indicated that the amplitude of the N2 wave of the CAEP in the left ear (not right ear) was significantly influenced by standard deviation of normal-to-normal RR-intervals (17.7%) and percentage of adjacent RR-intervals with a difference of duration greater than 50 milliseconds (25.3%) time domain HRV indices in the frequency protocol. In the duration protocol and in the left ear the latency of the P2 wave was significantly influenced by low (LF) (20.8%) and high frequency (HF) bands in normalized units (21%) and LF/HF ratio (22.4%) indices of HRV spectral analysis. The latency of the N2 wave was significantly influenced by LF (25.8%), HF (25.9%) and LF/HF (28.8%). In conclusion, we promote the supposition that resting heart rhythm is associated with thalamo-cortical, cortical-cortical and auditory cortex pathways involved with auditory processing in the right hemisphere.

Crosstalk between coagulation and inflammation in mastitis and metritis in dairy cows.

PubMed

Bobowiec, Ryszard; Wessely-Szponder, Joanna; Hola, Piotr

2009-06-01

Coagulation and inflammation are closely related as part of the mechanisms of host defence during a severe infection. The aim of this study was to investigate the relation between thrombin as a factor in both the coagulative and inflammatory processes and neutrophil secretory function on the basis of lactoferrin (LF), elastase and myeloperoxidase release in the course of mastitis and metritis in cows. Thrombin generation was measured on the basis of hydrolysis of SAR-PRO-ARG-pNA and lactoferrin concentration was estimated by an ELISA method. The greatest thrombin generation was observed in the metritis group (1.18 +/- 0.62 IU). The level of LF was the highest in the group of cows with mastitis (0.74 +/- 0.55 mg/ml) in the first phase of the disease. In the second phase of the diseases the level of serum LF in cows with mastitis diminished to the value of 0.41 +/- 0.16 mg/ml, whereas in cows with metritis the level of LF increased to 0.51 +/- 0.17 mg/ml. This study reveals that the excessive production of thrombin not only causes hypercoagulatory disorders but also exaggerates neutrophil function by the release of some enzymes which may play a destructive role during disseminated intravascular coagulation (DIC). These enzymes also inhibit anticoagulative systems, thus potentially worsening the course of the disease.

Effectiveness of Non-Lethal Capabilities in a Maritime Environment

DTIC Science & Technology

2006-09-01

demonstrates both the space filling properties for quantitative factors of the NOLH and the lack of correlation between the factors. 27 Figure 12 ...11 b. Optical Dazzler ........................................................................ 12 c...Warning Munitions................................................................. 12 2. Lethal Capabilities

Blue light treatment of Pseudomonas aeruginosa: Strong bactericidal activity, synergism with antibiotics and inactivation of virulence factors.

PubMed

Fila, Grzegorz; Kawiak, Anna; Grinholc, Mariusz Stanislaw

2017-08-18

Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies. Although blue light irradiation is a promising alternative approach, only limited and preliminary studies have described its effect on virulence factors. The current study aimed to investigate the effects of lethal and sub-lethal doses of blue light treatment (BLT) on P. aeruginosa virulence factors. We analyzed the inhibitory effects of blue light irradiation on the production/activity of several virulence factors. Lethal BLT inhibited the activity of pyocyanin, staphylolysin, pseudolysin and other proteases, but sub-lethal BLT did not affect the production/expression of proteases, phospholipases, and flagella- or type IV pili-associated motility. Moreover, a eukaryotic cytotoxicity test confirmed the decreased toxicity of blue light-treated extracellular P. aeruginosa fractions. Finally, the increased antimicrobial susceptibility of P. aeruginosa treated with sequential doses of sub-lethal BLT was demonstrated with a checkerboard test. Thus, this work provides evidence-based proof of the susceptibility of drug-resistant P. aeruginosa to BLT-mediated killing, accompanied by virulence factor reduction, and describes the synergy between antibiotics and sub-lethal BLT.

The Impact of Lymphatic Filariasis Mass Drug Administration Scaling Down on Soil-Transmitted Helminth Control in School-Age Children. Present Situation and Expected Impact from 2016 to 2020.

PubMed

Mupfasoni, Denise; Montresor, Antonio; Mikhailov, Alexei; King, Jonathan

2016-12-01

Lymphatic filariasis (LF) and soil-transmitted-helminths (STH) are co-endemic in 58 countries which are mostly in Africa and Asia. Worldwide, 486 million school-age children are considered at risk of both diseases. In 2000, the World Health Organization (WHO) established the global programme to eliminate LF by 2020. Since then, the LF elimination programme has distributed ivermectin or diethylcarbamazine citrate (DEC) in combination with albendazole, thereby also treating STH. Consequently, many school-age children have been treated for STH through the LF programme. As treatment targets towards the 2020 LF elimination goal are achieved, many countries are implementing the transmission assessment survey (TAS) and, if the LF prevalence is estimated to be less than 1%, scaling down mass drug administration (MDA). We analysed the 2014 data on preventive chemotherapy (PC) reported from LF STH co-endemic countries and projected the year and location of TAS expected to be conducted between 2016 and 2020 to assess the impact of this scaling down on STH PC. Eighty percent of all co-endemic countries that have already stopped LF MDA nationally were able to establish STH PC through schools. It is estimated that 14% of the total number of children presently covered by the LF programme is at risk of not continuing to receive PC for STH. In order to achieve and maintain the WHO 2020 goal for STH control, there is an urgent need to establish and reinforce school-based deworming programmes in countries scaling-down national LF elimination programmes.

Correlation Between Low Frequency Auroral Kilometric Radiation (AKR) and Auroral Structures

NASA Technical Reports Server (NTRS)

Paxamickas, Katherine A.; Green, James L.; Gallagher, Dennis L.; Boardsen, Scott; Mende, Stephen; Frey, Harald; Reinisch, Bodo W.

2005-01-01

Auroral Kilometric Radiation (AKR) is a radio wave emission that has long been associated with auroral activity. AKR is normally observed in the frequency range from -60 - 600 kHz. Low frequency AKR (or LF-AKR) events are characterized as a rapid extension of AKR related emissions to 30 kHz or lower in frequency for typically much less than 10 minutes. LF-AKR emissions predominantly occur within a frequency range of 20 kHz - 30 kHz, but there are LF-AKR related emissions that reach to a frequency of 5 kHz. This study correlates all instances of LF-AKR events during the first four years of observations from the IMAGE spacecraft's Radio Plasma Imager (WI) instrument with auroral observations from the wideband imaging camera (WIC) onboard IMAGE. The correlation between LF-AKR occurrence and WIC auroral observations shows that in the 295 confirmed cases of LF-AKR emissions, bifurcation of the aurora is seen in 74% of the cases. The bifurcation is seen in the dusk and midnight sectors of the auroral oval, where AKR is believed to be generated. The polarization of these LF-AKR emissions has yet to be identified. Although LF-AKR may not be the only phenomena correlated with bifurcated auroral structures, bifurcation will occur in most instances when LF-AKR is observed. The LF-AKR emissions may be an indicator of specific auroral processes sometimes occurring during storm-time conditions in which field-aligned density cavities extend a distance of perhaps 5-6 RE tailward from the Earth for a period of 10 minutes or less.

Quantum Field Theory in Two Dimensions: Light-front Versus Space-like Solutions

NASA Astrophysics Data System (ADS)

Martinovic̆, L'ubomír

2017-07-01

A few non-perturbative topics of quantum field theory in D=1+1 are studied in both the conventional (SL) and light-front (LF) versions. First, we give a concise review of the recently proposed quantization of the two-dimensional massless LF fields. The LF version of bosonization follows in a simple and natural way including the bosonized form of the Thirring model. As a further application, we demonstrate the closeness of the 2D massless LF quantum fields to conformal field theory (CFT). We calculate several correlation functions including those between the components of the LF energy-momentum tensor and derive the LF version of the Virasoro algebra. Using the Euclidean time variable, we can immediately transform calculated quantities to the (anti)holomorphic form. The results found are in agreement with those from CFT. Finally, we show that the proposed framework provides us with the elements needed for an independent LF study of exactly solvable models. We compute the non-perturbative correlation functions from the exact operator solution of the LF Thirring model and compare it to the analogous results in the SL theory. While the vacuum effects are automatically taken into account in the LF case, the non-trivial vacuum structure has to be incorported by an explicit diagonalization of the SL Hamiltonians, to obtain the equivalently complete solution.

GPU simulation of nonlinear propagation of dual band ultrasound pulse complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kvam, Johannes, E-mail: johannes.kvam@ntnu.no; Angelsen, Bjørn A. J., E-mail: bjorn.angelsen@ntnu.no; Elster, Anne C., E-mail: elster@ntnu.no

In a new method of ultrasound imaging, called SURF imaging, dual band pulse complexes composed of overlapping low frequency (LF) and high frequency (HF) pulses are transmitted, where the frequency ratio LF:HF ∼ 1 : 20, and the relative bandwidth of both pulses are ∼ 50 − 70%. The LF pulse length is hence ∼ 20 times the HF pulse length. The LF pulse is used to nonlinearly manipulate the material elasticity observed by the co-propagating HF pulse. This produces nonlinear interaction effects that give more information on the propagation of the pulse complex. Due to the large difference inmore » frequency and pulse length between the LF and the HF pulses, we have developed a dual level simulation where the LF pulse propagation is first simulated independent of the HF pulse, using a temporal sampling frequency matched to the LF pulse. A separate equation for the HF pulse is developed, where the the presimulated LF pulse modifies the propagation velocity. The equations are adapted to parallel processing in a GPU, where nonlinear simulations of a typical HF beam of 10 MHz down to 40 mm is done in ∼ 2 secs in a standard GPU. This simulation is hence very useful for studying the manipulation effect of the LF pulse on the HF pulse.« less

Formulation for Oral Delivery of Lactoferrin Based on Bovine Serum Albumin and Tannic Acid Multilayer Microcapsules

NASA Astrophysics Data System (ADS)

Kilic, Ece; Novoselova, Marina V.; Lim, Su Hui; Pyataev, Nikolay A.; Pinyaev, Sergey I.; Kulikov, Oleg A.; Sindeeva, Olga A.; Mayorova, Oksana A.; Murney, Regan; Antipina, Maria N.; Haigh, Brendan; Sukhorukov, Gleb B.; Kiryukhin, Maxim V.

2017-03-01

Lactoferrin (Lf) has considerable potential as a functional ingredient in food, cosmetic and pharmaceutical applications. However, the bioavailability of Lf is limited as it is susceptible to digestive enzymes in gastrointestinal tract. The shells comprising alternate layers of bovine serum albumin (BSA) and tannic acid (TA) were tested as Lf encapsulation system for oral administration. Lf absorption by freshly prepared porous 3 μm CaCO3 particles followed by Layer-by-Layer assembly of the BSA-TA shells and dissolution of the CaCO3 cores was suggested as the most efficient and harmless Lf loading method. The microcapsules showed high stability in gastric conditions and effectively protected encapsulated proteins from digestion. Protective efficiency was found to be 76 ± 6% and 85 ± 2%, for (BSA-TA)4 and (BSA-TA)8 shells, respectively. The transit of Lf along the gastrointestinal tract (GIT) of mice was followed in vivo and ex vivo using NIR luminescence. We have demonstrated that microcapsules released Lf in small intestine allowing 6.5 times higher concentration than in control group dosed with the same amount of free Lf. Significant amounts of Lf released from microcapsules were then absorbed into bloodstream and accumulated in liver. Suggested encapsulation system has a great potential for functional foods providing lactoferrin.

Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

PubMed Central

Cutone, Antimo; Lepanto, Maria Stefania; Paesano, Rosalba; Valenti, Piera

2017-01-01

Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 μg instead of 1–2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes. PMID:28914813

Effects of space flight factors on Drosophila.

PubMed

Dubinin, N P; Glembotsky, Y L; Vaulina, E N; Grozdova, T Y; Kamshilova, E M; Ivaschenko, N I; Kholikova, I A; Nechitailo, G S; Mashinsky, A L; Iordanishvili, E K

1973-01-01

Drosophila melanogaster flies of strain D-32 were exposed aboard the Soyuz 10 spaceship. An insert with a nutritional medium and insects was placed in a small on-board thermostat (Biotherm II) providing a constant temperature (24 degrees C +/- 1 degree) for Drosophila development. The frequency of dominant lethals was determined in the females. Dominant, autosomal and sex-linked recessive lethals were estimated in hatching virgin males and females; the time of hatching was rigorously fixed. Sex-linked recessive lethals were related to certain stages of gametogenesis. The 1-5 oocyte stage showed an increased sensitivity to space-flight factors as regards the frequency of both dominant and recessive lethals.

78 FR 66945 - Proposed Collection; 60-Day Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

... Comment request: Gulf Long-Term Follow-Up Study (GuLF STUDY) Summary: In compliance with the requirement... days of the date of this publication. Proposed Collection: Gulf Long-Term Follow-Up Study (GuLF STUDY... GuLF STUDY is to investigate potential short- and long-term health effects associated with oil spill...

Research and development on lactoferrin and its derivatives in China from 2011-2015.

PubMed

Wang, Xiao; Wang, Xiumin; Hao, Ya; Teng, Da; Wang, Jianhua

2017-02-01

Lactoferrin (Lf), a multifunctional glycoprotein, is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. Lactoferricin (Lfcin) is located in the N-terminal region of this protein. In this review, the current state of research into Lf and Lfcin in China is described. Searching with HistCite software in Web Sci located 118 papers published by Chinese researchers from 2011-2015, making China one of the top 3 producers of Lf research and development in the world. The biological functions of Lf and Lfcin are discussed, including antibacterial, antiviral, antifungal, anticarcinogenic, and anti-inflammatory activities; targeted drug delivery, induction of neurocyte, osteoblast, and tenocyte growth, and possible mechanisms of action. The preparation and heterologous expression of Lf in animals, bacteria, and yeast are discussed in detail. Five Lf-related food additive factories and 9 Lf-related health food production companies are certified by the China Food and Drug Administration (CFDA). The latest progress in the generation of transgenic livestock in China, the safety of the use of transgenic animals, and future prospects for the uses of Lf and Lfcin are also covered.

Nutritional composition analysis of meat from human lactoferrin transgenic bulls.

PubMed

Zhao, Jie; Xu, Jianxiang; Wang, Jianwu; Li, Ning

2013-01-01

Transgenic technology has many potential advantages in food production. However, the transgenic technology process may influence the composition of food products derived from genetically engineered (GE) animals, which may be adverse to human health. Therefore, it is very important to research the compositions of GE animal products. Here, we analyzed the compositions of meat from the offspring of human lactoferrin (hLF) transgenic cows, which can express human lactoferrin proteins in their mammary gland. Six hLF transgenic bulls and three wide-type (WT) bulls, 10 months of age, were slaughtered for meat composition analysis. To determine the comparative health of hLF bulls for meat analysis, hematological analyses, organ/body weight analyses and pathology analyses were conducted. Results of the meat analysis show that there were no significant differences in the hematological parameters, organ/body weight ratios of hLF and WT bulls (P>0.05), and histopathological examination of the main organs of hLF bulls revealed no abnormalities. Nutrient parameters of meat compositions of hLF and WT bulls did not show any significant differences (P>0.05). All of these results suggest that the hLF transgene did not have an impact on the meat nutrient compositions of hLF bulls.

A novel protein tyrosine phosphatase like phytase from Lactobacillus fermentum NKN51: Cloning, characterization and application in mineral release for food technology applications.

PubMed

Sharma, Rekha; Kumar, Piyush; Kaushal, Vandana; Das, Rahul; Kumar Navani, Naveen

2018-02-01

A novel protein tyrosine phosphatase like phytase (PTPLP), designated as PhyLf from probiotic bacterium Lactobacillus fermentum NKN51 was identified, cloned, expressed and characterized. The recombinant PhyLf showed specific activity of 174.5 U/mg. PhyLf exhibited strict specificity towards phytate and optimum temperature at 60 °C, pH 5.0 and ionic strength of 100 mM. K m and K cat of PhyLf for phytate were 0.773 mM and 84.31 s -1 , respectively. PhyLf exhibited high resistance against oxidative inactivation. PhyLf shares no homology, sans the active site with reported PTLPs, warranting classification as a new subclass. Dephytinization of durum wheat and finger millet under in vitro gastrointestinal conditions using PhyLf enhanced the bioaccessibility of mineral ions. Probiotic origin, phytate specificity, resistance to oxidative environment and gastric milieu coupled with ability to release micronutrients are unique properties of PhyLf which present a strong case for its use in ameliorating nutritional value of cereals and animal feed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interference of the antimicrobial peptide lactoferricin B with the action of various antibiotics against Escherichia coli and Staphylococcus aureus.

PubMed

Vorland, L H; Osbakk, S A; Perstølen, T; Ulvatne, H; Rekdal, O; Svendsen, J S; Gutteberg, T J

1999-01-01

The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the interaction of lactoferricin of bovine origin, Lf-cin B, with the antibiotics penicillin G, vancomycin, gentamicin, colistin, D-cycloserine and erythromycin against E. coli ATCC 25922 and Staphylococcus aureus ATCC 25923. We demonstrated synergism between Lf-cin B and erythromycin against E. coli, and partial synergism between Lf-cin B and penicillin G, vancomycin and gentamicin against E. coli. Only penicillin G acted in partial synergism with Lf-cin B against S. aureus. Lf-cin B antagonized vancomycin and gentamicin against S. aureus in low concentration. We conclude that Lf-cin B may facilitate the uptake of antibiotics across the cell envelope.

Global transcriptome analysis of the maize (Zea mays L.) inbred line 08LF during leaf senescence initiated by pollination-prevention.

PubMed

Wu, Liancheng; Li, Mingna; Tian, Lei; Wang, Shunxi; Wu, Liuji; Ku, Lixia; Zhang, Jun; Song, Xiaoheng; Liu, Haiping; Chen, Yanhui

2017-01-01

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention.

Impacts of Electric Propulsion Systems on Submarine Design

DTIC Science & Technology

1989-06-01

in oersteds D = the density of the steel in grams per cubic centimeter p = the elec" .,; al resistivity of the steel in microohm-centimeters N = the...Condition Al (Sum W1-W7) 4138.64 144.09 15.24 Lead Ballast 413.86 142.50 13.70 Condition A 4552.50 143.95 15.1 Variable Load Weights 209.53 87.46 9.86...fscanf(fp, "%lf", &lr); fscanf(fp, *W%lf?, &vol); fscanf(fp, "%lf", &wt.); fac~ azif (f p, "%lf" &ph); fscant (fp, "%If, &pe); fscanf(fp, "%lf" &i2r

Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats

NASA Astrophysics Data System (ADS)

Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

2016-04-01

The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate ( r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM-1 s-1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly showed the retention of Lf-M-PAEEP-PLLA-NPs in tumor tissues. The results from the in vitro and in vivo MRI indicated that Lf-M-PAEEP-PLLA-NPs possessed strong, long-lasting, tumor targeting, and enhanced tumor MRI contrast ability. Lf-M-PAEEP-PLLA-NPs represent a promising nano-sized MRI contrast agent for brain glioma targeting MRI.

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans

PubMed Central

Porter, Bradley; van Duijvenboden, Stefan; Bishop, Martin J.; Orini, Michele; Claridge, Simon; Gould, Justin; Sieniewicz, Benjamin J.; Sidhu, Baldeep; Razavi, Reza; Rinaldi, Christopher A.; Gill, Jaswinder S.; Taggart, Peter

2018-01-01

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans. Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n = 11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs = 0.933, p < 0.001), LF-ARI and LF-SBP (rs = 0.681, p = 0.001) and between LF-ARI and LF-dP/dtmax (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1 Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans. PMID:29670531

75 FR 77880 - Proposed Collection; Comment Request; GuLF Worker Study: Gulf Long-Term Follow-Up Study for Oil...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... Request: New. Need and Use of Information Collection: The purpose of the GuLF Study is to investigate... Request; GuLF Worker Study: Gulf Long-Term Follow-Up Study for Oil Spill Clean-Up Workers and Volunteers... instruments display a currently valid OMB control number. Proposed Collection Title: GuLF Worker Study: Gulf...

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection.

PubMed

Branco, Luis M; Grove, Jessica N; Boisen, Matt L; Shaffer, Jeffrey G; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Grant, Donald S; Garry, Robert F

2011-10-24

Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF.

Variations of the VLF/LF signals during seismic activity in Japan in November 2016

NASA Astrophysics Data System (ADS)

Rozhnoi, Alexander; Solovieva, Maria; Levin, Boris; Chebrov, Danila; Hayakawa, Masashi; Fedun, Viktor

2017-04-01

The measurements of the very low and low frequency (VLF/LF) signals at the Petropavlovsk-Kamchatsky and Yuzhno-Sakhalinsk stations were used for the analysis in connection with two underwater earthquakes which occurred near Japan in November 2016. The first earthquake with M=6.1 (depth 42 km) happened on 11 November. The second earthquake was recorded on 21 November with M=6.9 (depth 11 km) and had series of aftershocks with M up to 5.6 (USGS/NEIC). The significant negative nighttime amplitude anomalies were found for two sub-ionospheric paths: NWC-Petropavlovsk-Kamchatsky and JJY-Yuzhno-Sakhalinsk during about a week in case of the first earthquake. The anomalies of signal in the path JJY-Petropavlovsk-Kamchatsky were observed during 4-5 days before the second earthquake and during 3 days after it. Taking into account the possible influence of other factors which can produce perturbations in VLF/LF signals (geomagnetic storm, proton burst and the relativistic electron fluxes, as well as atmospheric parameters), also using control paths, we may conclude that observed anomalies very likely were caused by impending earthquakes.

Using Rasch Analysis to Validate the Motor Activity Log and the Lower Functioning Motor Activity Log in Patients With Stroke.

PubMed

Chuang, I-Ching; Lin, Keh-Chung; Wu, Ching-Yi; Hsieh, Yu-Wei; Liu, Chien-Ting; Chen, Chia-Ling

2017-10-01

The Motor Activity Log (MAL) and Lower-Functioning MAL (LF-MAL) are used to assess the amount of use of the more impaired arm and the quality of movement during activities in real-life situations for patients with stroke. This study used Rasch analysis to examine the psychometric properties of the MAL and LF-MAL in patients with stroke. This is a methodological study. The MAL and LF-MAL include 2 scales: the amount of use (AOU) and the quality of movement (QOM). Rasch analysis was used to examine the unidimensionality, item difficulty hierarchy, targeting, reliability, and differential item functioning (DIF) of the MAL and LF-MAL. A total of 403 patients with mild or moderate stroke completed the MAL, and 134 patients with moderate/severe stroke finished the LF-MAL. Evidence of disordered thresholds and poor model fit were found both in the MAL and LF-MAL. After the rating categories were collapsed and misfit items were deleted, all items of the revised MAL and LF-MAL exhibited ordering and constituted unidimensional constructs. The person-item map showed that these assessments were difficult for our participants. The person reliability coefficients of these assessments ranged from .79 to .87. No items in the revised MAL and LF-MAL exhibited bias related to patients' characteristics. One limitation is the recruited patients, who have relatively high-functioning ability in the LF-MAL. The revised MAL and LF-MAL are unidimensional scales and have good reliability. The categories function well, and responses to all items in these assessments are not biased by patients' characteristics. However, the revised MAL and LF-MAL both showed floor effect. Further study might add easy items for assessing the performance of activity in real-life situations for patients with stroke. © 2017 American Physical Therapy Association

Lassa Fever in Post-Conflict Sierra Leone

PubMed Central

Hartnett, Jessica N.; Levy, Danielle C.; Yenni, Rachael E.; Moses, Lina M.; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J.; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J.; Jones, Abigail B.; Illick, Megan M.; Kulakosky, Peter C.; Haislip, Allyson M.; Bishop, Christopher M.; Elliot, Deborah H.; Brown, Bethany L.; Zhu, Hu; Hastie, Kathryn M.; Andersen, Kristian G.; Gire, Stephen K.; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B.; Spence, Jennifer S.; Cross, Robert W.; Geisbert, Joan B.; Folarin, Onikepe A.; Happi, Christian T.; Pitts, Kelly R.; Geske, F. Jon; Geisbert, Thomas W.; Saphire, Erica Ollmann; Robinson, James E.; Wilson, Russell B.; Sabeti, Pardis C.; Henderson, Lee A.; Khan, S. Humarr; Bausch, Daniel G.; Branco, Luis M.; Garry, Robert F.

2014-01-01

Background Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF. PMID:24651047

Relationships among low-frequency local field potentials, spiking activity, and three-dimensional reach and grasp kinematics in primary motor and ventral premotor cortices

PubMed Central

Vargas-Irwin, Carlos E.; Truccolo, Wilson; Donoghue, John P.

2011-01-01

A prominent feature of motor cortex field potentials during movement is a distinctive low-frequency local field potential (lf-LFP) (<4 Hz), referred to as the movement event-related potential (mEP). The lf-LFP appears to be a global signal related to regional synaptic input, but its relationship to nearby output signaled by single unit spiking activity (SUA) or to movement remains to be established. Previous studies comparing information in primary motor cortex (MI) lf-LFPs and SUA in the context of planar reaching tasks concluded that lf-LFPs have more information than spikes about movement. However, the relative performance of these signals was based on a small number of simultaneously recorded channels and units, or for data averaged across sessions, which could miss information of larger-scale spiking populations. Here, we simultaneously recorded LFPs and SUA from two 96-microelectrode arrays implanted in two major motor cortical areas, MI and ventral premotor (PMv), while monkeys freely reached for and grasped objects swinging in front of them. We compared arm end point and grip aperture kinematics′ decoding accuracy for lf-LFP and SUA ensembles. The results show that lf-LFPs provide enough information to reconstruct kinematics in both areas with little difference in decoding performance between MI and PMv. Individual lf-LFP channels often provided more accurate decoding of single kinematic variables than any one single unit. However, the decoding performance of the best single unit among the large population usually exceeded that of the best single lf-LFP channel. Furthermore, ensembles of SUA outperformed the pool of lf-LFP channels, in disagreement with the previously reported superiority of lf-LFP decoding. Decoding results suggest that information in lf-LFPs recorded from intracortical arrays may allow the reconstruction of reach and grasp for real-time neuroprosthetic applications, thus potentially supplementing the ability to decode these same features from spiking populations. PMID:21273313

Enhancement of endotoxin neutralization by coupling of a C12-alkyl chain to a lactoferricin-derived peptide

PubMed Central

2004-01-01

Antibacterial peptide acylation, which mimics the structure of the natural lipopeptide polymyxin B, increases antimicrobial and endotoxin-neutralizing activities. The interaction of the lactoferricin-derived peptide LF11 and its N-terminally acylated analogue, lauryl-LF11, with different chemotypes of bacterial lipopolysaccharide (LPS Re, Ra and smooth S form) was investigated by biophysical means and was related to the peptides' biological activities. Both peptides exhibit high antibacterial activity against the three strains of Salmonella enterica differing in the LPS chemotype. Lauryl-LF11 has one order of magnitude higher activity against Re-type, but activity against Ra- and S-type bacteria is comparable with that of LF11. The alkyl derivative peptide lauryl-LF11 shows a much stronger inhibition of the LPS-induced cytokine induction in human mononuclear cells than LF11. Although peptide–LPS interaction is essentially of electrostatic nature, the lauryl-modified peptide displays a strong hydrophobic component. Such a feature might then explain the fact that saturation of the peptide binding takes place at a much lower peptide/LPS ratio for LF11 than for lauryl-LF11, and that an overcompensation of the negative LPS backbone charges is observed for lauryl-LF11. The influence of LF11 on the gel-to-liquid-crystalline phase-transition of LPS is negligible for LPS Re, but clearly fluidizing for LPS Ra. In contrast, lauryl-LF11 causes a cholesterol-like effect in the two chemotypes, fluidizing in the gel and rigidifying of the hydrocarbon chains in the liquid-crystalline phase. Both peptides convert the mixed unilamellar/non-lamellar aggregate structure of lipid A, the ‘endotoxic principle’ of LPS, into a multilamellar one. These data contribute to the understanding of the mechanisms of the peptide-mediated neutralization of endotoxin and effect of lipid modification of peptides. PMID:15344905

Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1.

PubMed

Elatrech, Imen; Marzaioli, Viviana; Boukemara, Hanane; Bournier, Odile; Neut, Christel; Darfeuille-Michaud, Arlette; Luis, José; Dubuquoy, Laurent; El-Benna, Jamel; My-Chan Dang, Pham; Marie, Jean-Claude

2015-05-01

Increased reactive oxygen species (ROS) production is associated with inflamed ileal lesions in Crohn's disease colonized by pathogenic adherent-invasive Escherichia coli LF82. We investigated whether such ileal bacteria can modulate ROS production by epithelial cells, thus impacting on inflammation and mucin expression. Ileal bacteria from patients with Crohn's disease were incubated with cultured epithelial T84 cells, and ROS production was assayed using the luminol-amplified chemiluminescence method. The gentamicin protection assay was used for bacterial invasion of T84 cell. The expression of NADPH oxidase (NOX) subunits, mucin, and IL-8 was analyzed by quantitative real-time PCR and Western blots. Involvement of NOX and ROS was analyzed using diphenyleneiodonium (DPI) and N-acetylcysteine (NAC). Among different bacteria tested, only LF82 induced an increase of ROS production by T84 cells in a dose-dependent manner. This response was inhibited by DPI and NAC. Heat- or ethanol-attenuated LF82 bacteria and the mutant LF82ΔFimA, which does not express pili type 1 and poorly adheres to epithelial cells, did not induce the oxidative response. The LF82-induced oxidative response coincides with its invasion in T84 cells, and both processes were inhibited by DPI. Also, we observed an increased expression of NOX1 and NOXO1 in response to LF82 bacteria versus the mutant LF82ΔFimA. Furthermore, LF82 inhibited mucin gene expression (MUC2 and MUC5AC) in T84 cells while increasing the chemotactic IL-8 expression, both in a DPI-sensitive manner. Adherent-invasive E. coli LF82 induced ROS production by intestinal NADPH oxidase and altered mucin and IL-8 expression, leading to perpetuation of inflammatory lesions in Crohn's disease.

Oral lactoferrin protects against experimental candidiasis in mice.

PubMed

Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

2015-01-01

To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

Prebiotic effects of bovine lactoferrin on specific probiotic bacteria.

PubMed

Chen, Po-Wen; Liu, Zhen-Shu; Kuo, Tai-Chen; Hsieh, Min-Chi; Li, Zhe-Wei

2017-04-01

Bovine lactoferrin (bLf) is a natural iron-binding protein and it has been suggested to be a prebiotic agent, but this finding remains inconclusive. This study explores the prebiotic potential of bLf in 14 probiotics. Initially, bLf (1-32 mg/mL) treatment showed occasional and slight prebiotic activity in several probiotics only during the late experimental period (48, 78 h) at 37 °C. We subsequently supposed that bLf exerts stronger prebiotic effects when probiotic growth has been temperately retarded. Therefore, we incubated the probiotics at different temperatures, namely 37 °C, 28 °C, room temperature (approximately 22-24 °C), and 22 °C, to retard or inhibit their growth. As expected, bLf showed more favorable prebiotic activity in several probiotics when their growth was partially retarded at room temperature. Furthermore, at 22 °C, the growth of Bifidobacterium breve, Lactobacillus coryniformis, L. delbrueckii, L. acidophilus, B. angulatum, B. catenulatum, and L. paraplantarum were completely blocked. Notably, these probiotics started regrowing in the presence of bLf (1-32 mg/mL) in a significant and dose-dependent manner. Accordingly, bLf significantly increased the growth of Pediococcus pentosaceus, L. rhamnosus, and L. paracasei (BCRC 17483; a locally isolated strain) when their growth was retarded by incubation at 22 °C. In conclusion, bLf showed inconsistent prebiotic activity in the 14 probiotics at 37 °C, but revealed strong prebiotic activity in 10 probiotic strains at 22 °C. Therefore, this study enables determining additional roles of Lf in probiotic strains, which can facilitate developing novel combinational approaches by simultaneously using Lf and specific probiotics.

77 FR 32009 - Airworthiness Directives; Honeywell International, Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... Airworthiness Directives; Honeywell International, Inc. Turbofan Engines AGENCY: Federal Aviation Administration... Honeywell International, Inc. ALF502L-2C; ALF502R-3; ALF502R-3A; ALF502R-5; LF507-1F; and LF507-1H turbofan...; ALF502R-3A; ALF502R-5; LF507-1F; and LF507- 1H turbofan engines, installed on airplanes of U.S. registry...

Urban lymphatic filariasis.

PubMed

Simonsen, Paul E; Mwakitalu, Mbutolwe E

2013-01-01

Lymphatic filariasis (LF) is a disabling and disfiguring disease resulting from a mosquito-borne parasitic infection. It is a major public health problem in many countries with a warm climate. Research and control activities have mainly focused on LF in rural areas where it also has its major impact. However, with rapid and unplanned growth of cities in the developing world, there is a need also to consider LF transmission and control in urban settings. Here, we review currently available knowledge on urban LF and the environmental and socio-economic basis for its occurrence. Among the three parasite species causing LF in humans, only Wuchereria bancrofti has been documented to have a significant potential for urban transmission. This is primarily because one of its vectors, Culex quinquefasciatus, thrives and proliferates excessively in crowded city areas with poor sanitary, sewerage and drainage facilities. For this reason, urban LF also often shows a marked focality in distribution, with most cases clustered in areas inhabited by the less privileged city populations. More knowledge on urban LF is needed, in particular on its socio-economic and human behavioural context, on the potential for transmission in regions where other LF vector species predominate, and on rapid methods for identification and mapping of risk areas, to provide a strong evidence base for its control.

Factors Affecting the Nonlinear Force Versus Distraction Height Curves in an In Vitro C5-C6 Anterior Cervical Distraction Model.

PubMed

Wen, Junxiang; Xu, Jianwei; Li, Lijun; Yang, Mingjie; Pan, Jie; Chen, Deyu; Jia, Lianshun; Tan, Jun

2017-06-01

In vitro biomechanical study of cervical intervertebral distraction. To investigate the forces required for distraction to different heights in an in vitro C5-C6 anterior cervical distraction model, focusing on the influence of the intervertebral disk, posterior longitudinal ligament (PLL), and ligamentum flavum (LF). No previous studies have reported on the forces required for distraction to various heights or the factors resisting distraction in anterior cervical discectomy and fusion. Anterior cervical distraction at C5-C6 was performed in 6 cadaveric specimens using a biomechanical testing machine, under 4 conditions: A, before disk removal; B, after disk removal; C, after disk and PLL removal; and D, after disk and PLL removal and cutting of the LF. Distraction was performed from 0 to 10 mm at a constant velocity (5 mm/min). Force and distraction height were recorded automatically. The force required increased with distraction height under all 4 conditions. There was a sudden increase in force required at 6-7 mm under conditions B and C, but not D. Under condition A, distraction to 5 mm required a force of 268.3±38.87 N. Under conditions B and C, distraction to 6 mm required <15 N, and further distraction required dramatically increased force, with distraction to 10 mm requiring 115.4±10.67 and 68.4±9.67 N, respectively. Under condition D, no marked increase in force was recorded. Distraction of the intervertebral space was much easier after disk removal. An intact LF caused a sudden marked increase in the force required for distraction, possibly indicating the point at which the LF was fully stretched. This increase in resistance may help to determine the optimal distraction height to avoid stress to the endplate spacer.

High Efficiency Organic/Silicon-Nanowire Hybrid Solar Cells: Significance of Strong Inversion Layer

PubMed Central

Yu, Xuegong; Shen, Xinlei; Mu, Xinhui; Zhang, Jie; Sun, Baoquan; Zeng, Lingsheng; Yang, Lifei; Wu, Yichao; He, Hang; Yang, Deren

2015-01-01

Organic/silicon nanowires (SiNWs) hybrid solar cells have recently been recognized as one of potentially low-cost candidates for photovoltaic application. Here, we have controllably prepared a series of uniform silicon nanowires (SiNWs) with various diameters on silicon substrate by metal-assisted chemical etching followed by thermal oxidization, and then fabricated the organic/SiNWs hybrid solar cells with poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS). It is found that the reflective index of SiNWs layer for sunlight depends on the filling ratio of SiNWs. Compared to the SiNWs with the lowest reflectivity (LR-SiNWs), the solar cell based on the SiNWs with low filling ratio (LF-SiNWs) has a higher open-circuit voltage and fill factor. The capacitance-voltage measurements have clarified that the built-in potential barrier at the LF-SiNWs/PEDOT:PSS interface is much larger than that at the LR-SiNWs/PEDOT one, which yields a strong inversion layer generating near the silicon surface. The formation of inversion layer can effectively suppress the carrier recombination, reducing the leakage current of solar cell, and meanwhile transfer the LF-SiNWs/PEDOT:PSS device into a p-n junction. As a result, a highest efficiency of 13.11% is achieved for the LF-SiNWs/PEDOT:PSS solar cell. These results pave a way to the fabrication of high efficiency organic/SiNWs hybrid solar cells. PMID:26610848

The Luminosity Function of Fermi-detected Flat-Spectrum Radio Quasars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajello, M.; Shaw, M.S.; Romani, R.W.

2012-04-16

Fermi has provided the largest sample of {gamma}-ray selected blazars to date. In this work we use a complete sample of FSRQs detected during the first year of operation to determine the luminosity function (LF) and its evolution with cosmic time. The number density of FSRQs grows dramatically up to redshift {approx}0.5-2.0 and declines thereafter. The redshift of the peak in the density is luminosity dependent, with more luminous sources peaking at earlier times; thus the LF of {gamma}-ray FSRQs follows a luminosity-dependent density evolution similarly to that of radio-quiet AGN. Also using data from the Swift Burst Alert Telescopemore » we derive the average spectral energy distribution of FSRQs in the 10 keV-100GeV band and show that there is no correlation of the peak {gamma}-ray luminosity with {gamma}-ray peak frequency. The coupling of the SED and LF allows us to predict that the contribution of FSRQs to the Fermi isotropic {gamma}-ray background is 9.3{sub -1.0}{sup +1.6}% ({+-}3% systematic uncertainty) in the 0.1-100GeV band. Finally we determine the LF of unbeamed FSRQs, finding that FSRQs have an average Lorentz factor of {gamma} = 11.7{sub -2.2}{sup +3.3}, that most are seen within 5{sup o} of the jet axis, and that they represent only {approx}0.1% of the parent population.« less

High Efficiency Organic/Silicon-Nanowire Hybrid Solar Cells: Significance of Strong Inversion Layer.

PubMed

Yu, Xuegong; Shen, Xinlei; Mu, Xinhui; Zhang, Jie; Sun, Baoquan; Zeng, Lingsheng; Yang, Lifei; Wu, Yichao; He, Hang; Yang, Deren

2015-11-27

Organic/silicon nanowires (SiNWs) hybrid solar cells have recently been recognized as one of potentially low-cost candidates for photovoltaic application. Here, we have controllably prepared a series of uniform silicon nanowires (SiNWs) with various diameters on silicon substrate by metal-assisted chemical etching followed by thermal oxidization, and then fabricated the organic/SiNWs hybrid solar cells with poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) ( PSS). It is found that the reflective index of SiNWs layer for sunlight depends on the filling ratio of SiNWs. Compared to the SiNWs with the lowest reflectivity (LR-SiNWs), the solar cell based on the SiNWs with low filling ratio (LF-SiNWs) has a higher open-circuit voltage and fill factor. The capacitance-voltage measurements have clarified that the built-in potential barrier at the LF-SiNWs/ PSS interface is much larger than that at the LR-SiNWs/PEDOT one, which yields a strong inversion layer generating near the silicon surface. The formation of inversion layer can effectively suppress the carrier recombination, reducing the leakage current of solar cell, and meanwhile transfer the LF-SiNWs/ PSS device into a p-n junction. As a result, a highest efficiency of 13.11% is achieved for the LF-SiNWs/ PSS solar cell. These results pave a way to the fabrication of high efficiency organic/SiNWs hybrid solar cells.

77 FR 14312 - Airworthiness Directives; Honeywell International, Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... International, Inc. Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... Honeywell International, Inc. ALF502L-2C; ALF502R-3; ALF502R-3A; ALF502R-5; LF507-1F; and LF507-1H turbofan...; ALF502R-3A; ALF502R-5; LF507-1F; and LF507-1H turbofan engines, installed on airplanes of U.S. registry...

Understanding the cryptic nature of Lassa fever in West Africa.

PubMed

Gibb, Rory; Moses, Lina M; Redding, David W; Jones, Kate E

2017-09-01

Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa's poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions. Although the recent increase in LF case reports is likely due to improved surveillance, recent studies suggest that future socio-ecological changes in West Africa may drive increases in LF burden. Future research should focus on the geographical distribution and disease burden of LF, in order to improve its integration into public policy and disease control strategies.

High-Level Expression of Recombinant Bovine Lactoferrin in Pichia pastoris with Antimicrobial Activity

PubMed Central

Iglesias-Figueroa, Blanca; Valdiviezo-Godina, Norberto; Siqueiros-Cendón, Tania; Sinagawa-García, Sugey; Arévalo-Gallegos, Sigifredo; Rascón-Cruz, Quintín

2016-01-01

In this study, bovine lactoferrin (bLf), an iron-binding glycoprotein considered an important nutraceutical protein because of its several properties, was expressed in Pichia pastoris KM71-H under AOX1 promoter control, using pJ902 as the recombinant plasmid. Dot blotting analysis revealed the expression of recombinant bovine lactoferrin (rbLf) in Pichia pastoris. After Bach fermentation and purification by molecular exclusion, we obtained an expression yield of 3.5 g/L of rbLf. rbLf and predominantly pepsin-digested rbLf (rbLfcin) demonstrated antibacterial activity against Escherichia coli (E. coli) BL21DE3, Staphylococcus aureus (S. aureus) FRI137, and, in a smaller percentage, Pseudomonas aeruginosa (Ps. Aeruginosa) ATCC 27833. The successful expression and characterization of functional rbLf expressed in Pichia pastoris opens a prospect for the development of natural antimicrobial agents produced recombinantly. PMID:27294912

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

PubMed

Sen, Tanusree; Cawthon, Carolina R; Ihde, Benjamin Thomas; Hajnal, Andras; DiLorenzo, Patricia M; de La Serre, Claire B; Czaja, Krzysztof

2017-05-01

Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation. © 2016.

Psychosocial influences on prisoner suicide: a case-control study of near-lethal self-harm in women prisoners.

PubMed

Marzano, Lisa; Hawton, Keith; Rivlin, Adrienne; Fazel, Seena

2011-03-01

We examined the psychosocial influences on female prisoner suicide by carrying out a study of near-lethal self-harm. We interviewed 60 women prisoners who had recently engaged in near-lethal self-harm (cases) and 60 others who had never carried out near-lethal acts in prison (controls) from all closed female prison establishments in England and Wales, using mixed quantitative and qualitative methods. We gathered information on socio-demographic and criminological variables, life events and childhood trauma, exposure to suicidal behaviour, contributory and precipitating factors for near-lethal self-harm, social support and psychological characteristics. While socio-demographic factors were only modestly associated with near-lethal self-harm, being on remand, in single cell accommodation, and reporting negative experiences of imprisonment were strong correlates. Recent life events and past trauma, including different forms of childhood abuse, were also significantly associated with near-lethal self-harm, as were a family history of suicide and high scores on measures of depression, aggression, impulsivity and hostility, and low levels of self-esteem and social support. Our findings underline the importance of both individual and prison-related factors for suicide in custody, and hence the need for a comprehensive approach to suicide prevention in women's prisons. Given the multiple needs of female prisoners at-risk of self-harm and suicide, complex psychosocial interventions are likely to be required, including interventions for abused and bereaved women, and initiatives to improve staff-prisoner relationships and reduce bullying. The findings of this research may provide insights into factors leading to suicidal behaviour in other forensic and institutional settings, such as detention centres and psychiatric hospitals, and may assist in developing suicide prevention policies for prisoners and other at-risk populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Coma Cluster Luminosity Function from Ultraviolet to Near-Infrared

NASA Astrophysics Data System (ADS)

Andreon, S.; Cuillandre, J.-C.; Pello, R.

The Coma cluster luminosity function (LF) from ultraviolet (2000 AA ) to the near-infrared (H band) is summarized. In the UV the LF is very steep, much steeper than in the optical. The steep Coma UV LF implies that faint and bright galaxies give similar contributions to the total UV flux and to the total metal production rate. The ComaUV LF is dominated in number and luminosity by blue galaxies, which are often faint in the optical. Therefore the Coma UV LF is dominated by star forming galaxies, not by massive and large galaxies. The optical Coma LF is relatively steep (alpha=-1.4) over the 11 magnitudes sampled, but its slope and shape depend on considered filter and magnitude. We found a clear steeping of the FL going from B to R bands, indicative of the presence of a large number of red dwarfs, as faint as three bright globular clusters. Furthermore, using Hubble Space Telescope images, we discover that blends of globular clusters, not resolved in individual components due to seeing, look like dwarf galaxies when observed from the ground and are numerous and bright. The existence of these fake extended sources increases the steepness of the LF at faint magnitudes, if not deal on. This concern affects previous deep probing of the luminosity function, but not the present work. The near-infrared LF wa s computed on a near-infrared selected sample of galaxies which photometry is complete down to the typical dwarf (M* +5) luminosity. The Coma LF can be described by a Schechter function with intermediate slope (alpha sim-1.3), plus a dip at MH~-22 mag. The shape of the Coma LF in H band is quite similar to th e one found in the B band. The similarity of the LF in the optical and H bands implies that in the central region of Coma there is no new population of galaxies which is too faint to be observed in the optical band (because dust enshrouded, for instance), down to the magnitudes of dwarfs. The exponential cut of the LF at the bright end is in good agreement with the one derived from shallower near-infrared samples o f galaxies, both in clusters and in the field. The faint end of the LF, reaching MH~-19 mag (roughly MB~ -15), is steep, but less than previously suggested from shallower near-infrared observations of an adjacent region in the Coma cluster.

Growth and tolerance of formula with lactoferrin in infants through one year of age: double-blind, randomized, controlled trial.

PubMed

Johnston, William H; Ashley, Claude; Yeiser, Michael; Harris, Cheryl L; Stolz, Suzanne I; Wampler, Jennifer L; Wittke, Anja; Cooper, Timothy R

2015-11-07

Human milk provides necessary macronutrients (protein, carbohydrate, fat) required for infant nutrition. Lactoferrin (Lf), a multifunctional iron-binding protein predominant in human milk, shares similar protein sequence, structure, and bioactivity with bovine Lf (bLf). This large-scale pediatric nutrition study was designed to evaluate growth and tolerance in healthy infants who received study formulas with bLf at concentrations within the range of mature human milk. In this multi-center, double-blind, parallel-designed, gender-stratified prospective study 480 infants were randomized to receive a marketed routine cow's milk-based infant formula (Control; n = 155) or one of two investigational formulas with bLf at 0.6 g/L (LF-0.6; n = 165) or 1.0 g/L (LF-1.0; n = 160) from 14-365 days of age. Investigational formulas also had a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) and adjusted arachidonic acid (ARA). The primary outcome was weight growth rate from 14-120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, 120, 180, 275, and 365 days of age. Parental recall of formula intake, tolerance, and stool characteristics was collected at each time point. Medically-confirmed adverse events were collected throughout the study period. There were no group differences in growth rate (g/day) from 14-120 days of age; 353 infants completed the study through 365 days of age ( 110; LF-0.6: 127; LF-1.0: 116). Few differences in growth, formula intake, and infant fussiness or gassiness were observed through 365 day of age. Group discontinuation rates and the overall group incidence of medically-confirmed adverse events were not significantly different. From 30 through 180 days of age, group differences in stool consistency (P < 0.005) were detected with softer stools for infants in the LF-0.6 and LF-1.0 groups versus CONTROL. Compared to the Control, infants who received investigational formulas with bLf and the prebiotic blend of PDX and GOS experienced a softer stooling pattern similar to that reported in breastfed infants. This study demonstrated routine infant formulas with bLf, a blend of PDX and GOS, and adjusted ARA were safe, well-tolerated, and associated with normal growth when fed to healthy term infants through 365 days of age. ClinicalTrials.gov NCT01122654 . Registered 10 May 2010.

Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues.

PubMed

Fischer, Romy; Debbabi, Hajer; Blais, Anne; Dubarry, Michel; Rautureau, Michèle; Boyaka, Prosper N; Tome, Daniel

2007-10-01

Lactoferrin is a glycoprotein with antimicrobial and immunoregulatory properties, which is found in milk, other external secretions, and in the secondary granules of neutrophils. The present study examined the time course of uptake and the pattern of tissue accumulation of bovine lactoferrin (bLf) following intragastric intubation of a single dose to adult naïve mice or to mice daily fed bLf for 4 weeks. Following ingestion, bLf was transferred from the intestine into peripheral blood in a form with intact molecular weight (80 kDa) and localized within 10 to 20 min after oral administration in the liver, kidneys, gall bladder, spleen, and brain of both groups of mice. Immunoreactive bLf could also be detected in the luminal contents of the stomach, small intestine and colon 1 h after intragastric intubation. Interestingly, serum and tissue accumulation of bLf was approximately 50% lower in mice chronically fed this protein than in those given only the single oral dose. Furthermore, significant levels of bLf-specific IgA and IgG antibodies as well as bLf-containing IgA- and IgG immune complexes were detected in mice chronically fed bLf but not in those fed only once. Taken together, these results indicate that bLf resists major proteolytic degradation in the intestinal lumen and is readily absorbed in an antigenic form in blood and various mouse tissues. Chronic ingestion of lactoferrin reduces its uptake, probably through mechanisms such as immune exclusion, which minimize potential harmful reactions to food products.

Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda.

PubMed

Shah, Maunank; Dowdy, David; Joloba, Moses; Ssengooba, Willy; Manabe, Yukari C; Ellner, Jerrold; Dorman, Susan E

2013-11-28

Xpert MTB/RIF ('Xpert') and urinary lateral-flow lipoarabinomannan (LF-LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert and LF-LAM for the detection of active TB among people living with HIV. Cost-effectiveness analysis using data from a comparative study of LF-LAM and Xpert, with a target population of HIV-infected individuals with signs/symptoms of TB in Uganda. A decision-analysis model compared multiple strategies for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the costs and DALY's averted for each algorithm. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER). Compared with an algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear-microscopy was a less effective strategy than Xpert replacement of smear-microscopy, but was less costly and also considered highly cost-effective (ICER $33 per DALY-averted) compared with continued usage of smear-microscopy alone. Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by HIV/ART costs and life-expectancy of patients after TB treatment. The addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected individuals is highly cost-effective compared with usage of either sputum smear-microscopy or Xpert alone.

Systematic review: Laparoscopic fundoplication for gastroesophageal reflux disease in partial responders to proton pump inhibitors

PubMed Central

Lundell, Lars; Bell, Martin; Ruth, Magnus

2014-01-01

AIM: To assess laparoscopic fundoplication (LF) in partial responders to proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD). METHODS: We systematically searched PubMed and Embase (1966-Dec 2011) for articles reporting data on LF efficacy in partial responders. Due to a lack of randomized controlled trials, observational studies were included. Of 558 articles screened, 17 were eligible for inclusion. Prevalence data for individual symptoms were collated across studies according to mutually compatible time points (before and/or after LF). Where suitable, prevalence data were presented as percentage of patients reporting symptoms of any frequency or severity. RESULTS: Due to a lack of standardized reporting of symptoms, the proportion of patients experiencing symptoms was recorded across studies where possible. After LF, the proportion of partial responders with heartburn was reduced from 93.1% (5 studies) to 3.8% (5 studies), with similar results observed for regurgitation [from 78.4% (4 studies) to 1.9% (4 studies)]. However, 10 years after LF, 35.8% (2 studies) of partial responders reported heartburn and 29.1% (1 study) reported regurgitation. The proportion using acid-suppressive medication also increased, from 8.8% (4 studies) in the year after LF to 18.2% (2 studies) at 10 years. In the only study comparing partial responders to PPI therapy with complete responders, higher symptom scores and more frequent acid-suppressive medication use were seen in partial responders after LF. CONCLUSION: GERD symptoms improve after LF, but subsequently recur, and acid-suppressive medication use increases. LF may be less effective in partial responders than in complete responders. PMID:24574753

Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection

PubMed Central

2011-01-01

Background Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Results Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Conclusion Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF. PMID:22023795

The 6th Meeting of the Global Alliance to Eliminate Lymphatic Filariasis: A half-time review of lymphatic filariasis elimination and its integration with the control of other neglected tropical diseases

PubMed Central

2010-01-01

The 6th Meeting of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF6) was held 1-3 June, 2010 in Seoul, Korea, with 150 participants from 38 countries. The year 2010 marks the midpoint between the first GAELF meeting, in 2000, and the World Health Organization (WHO) 2020 goal of global elimination of lymphatic filariasis (LF) as a public health problem. The theme of the meeting, "Half-time in LF Elimination: Teaming Up with Neglected Tropical Diseases (NTDs)," reflected significant integration of LF elimination programmes into a comprehensive initiative to control NTDs. Presentations on LF epidemiology, treatment, research, and programmes highlighted both accomplishments and remaining challenges. The WHO strategy to interrupt LF transmission is based on annual mass drug administration (MDA) using two-drug combinations. After mapping the geographic distribution of LF, MDA is implemented for ≥ 5 years, followed by a period of post-MDA surveillance, and, ultimately, verification of LF elimination. Morbidity management further reduces disease burden. Of 81 countries considered LF-endemic in 2000, 52 (64.2%) have begun MDA; 10 (12.3%) others with low-level transmission are unlikely to require MDA. In 2008, ~695 million people were offered treatment (51.7% of the at-risk population); ~496 million participated. Approximately 22 million people have been protected from LF infection and disease, with savings of ~US $24.2 billion. Morbidity management programmes have been implemented in 27 (33.3%) countries. Significant challenges to LF elimination remain. These include: initiating MDA in the remaining 19 countries that require it; achieving full geographic coverage in countries where MDA has started; finding alternative strategies to address the problem of Loa loa co-endemicity in Central Africa; developing strategies to treat urban populations; initiating and sustaining MDA in settings of armed conflict; developing refined guidelines and procedures for stopping MDA, for post-MDA surveillance, and for verifying the elimination of LF; and integrating morbidity management into all LF elimination programmes. Scientific research and enhanced advocacy for NTDs remain critical for addressing these challenges. GAELF6 was characterized by enthusiasm and recognition that "teaming up with NTDs" offers opportunities for new partnerships, fresh perspectives, enhanced advocacy, and greater programmatic integration in a rapidly changing global health environment. PMID:20961435

Identification of genomic regions that interact with a viable allele of the Drosophila protein tyrosine phosphatase corkscrew.

PubMed Central

Firth, L; Manchester, J; Lorenzen, J A; Baron, M; Perkins, L A

2000-01-01

Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of developmental decisions and processes. Among the molecules known to transduce the RTK-generated signal is the nonreceptor protein tyrosine phosphatase Corkscrew (Csw). Previously, Csw has been demonstrated to function throughout the Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso, Sevenless, EGF, and Breathless/FGF RTK pathways. While the biochemical function of Csw remains to be unambiguously elucidated, current evidence suggests that Csw plays more than one role during transduction of the RTK signal and, further, the molecular mechanism of Csw function differs depending upon the RTK in question. The isolation and characterization of a new, spontaneously arising, viable allele of csw, csw(lf), has allowed us to undertake a genetic approach to identify loci required for Csw function. The rough eye and wing vein gap phenotypes exhibited by adult flies homo- or hemizygous for csw(lf) has provided a sensitized background from which we have screened a collection of second and third chromosome deficiencies to identify 33 intervals that enhance and 21 intervals that suppress these phenotypes. We have identified intervals encoding known positive mediators of RTK signaling, e.g., drk, dos, Egfr, E(Egfr)B56, pnt, Ras1, rolled/MAPK, sina, spen, Src64B, Star, Su(Raf)3C, and vein, as well as known negative mediators of RTK signaling, e.g., aos, ed, net, Src42A, sty, and su(ve). Of particular interest are the 5 lethal enhancing intervals and 14 suppressing intervals for which no candidate genes have been identified. PMID:11014820

Identification of genomic regions that interact with a viable allele of the Drosophila protein tyrosine phosphatase corkscrew.

PubMed

Firth, L; Manchester, J; Lorenzen, J A; Baron, M; Perkins, L A

2000-10-01

Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of developmental decisions and processes. Among the molecules known to transduce the RTK-generated signal is the nonreceptor protein tyrosine phosphatase Corkscrew (Csw). Previously, Csw has been demonstrated to function throughout the Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso, Sevenless, EGF, and Breathless/FGF RTK pathways. While the biochemical function of Csw remains to be unambiguously elucidated, current evidence suggests that Csw plays more than one role during transduction of the RTK signal and, further, the molecular mechanism of Csw function differs depending upon the RTK in question. The isolation and characterization of a new, spontaneously arising, viable allele of csw, csw(lf), has allowed us to undertake a genetic approach to identify loci required for Csw function. The rough eye and wing vein gap phenotypes exhibited by adult flies homo- or hemizygous for csw(lf) has provided a sensitized background from which we have screened a collection of second and third chromosome deficiencies to identify 33 intervals that enhance and 21 intervals that suppress these phenotypes. We have identified intervals encoding known positive mediators of RTK signaling, e.g., drk, dos, Egfr, E(Egfr)B56, pnt, Ras1, rolled/MAPK, sina, spen, Src64B, Star, Su(Raf)3C, and vein, as well as known negative mediators of RTK signaling, e.g., aos, ed, net, Src42A, sty, and su(ve). Of particular interest are the 5 lethal enhancing intervals and 14 suppressing intervals for which no candidate genes have been identified.

Prevention of Suicidal Behavior in Prisons

PubMed Central

2016-01-01

Abstract. Background: Worldwide, prisoners are at high risk of suicide. Research on near-lethal suicide attempts can provide important insights into risk and protective factors, and inform suicide prevention initiatives in prison. Aims: To synthesize findings of research on near-lethal attempts in prisons, and consider their implications for suicide prevention policies and practice, in the context of other research in custody and other settings. Method: We searched two bibliographic indexes for studies in any language on near-lethal and severe self-harm in prisoners, supplemented by targeted searches over the period 2000–2014. We extracted information on risk factors descriptively. Data were not meta-analyzed owing to heterogeneity of samples and methods. Results: We identified eight studies reporting associations between prisoner near-lethal attempts and specific factors. The latter included historical, prison-related, and clinical factors, including psychiatric morbidity and comorbidity, trauma, social isolation, and bullying. These factors were also identified as important in prisoners' own accounts of what may have contributed to their attempts (presented in four studies). Conclusion: Factors associated with prisoners' severe suicide attempts include a range of potentially modifiable clinical, psychosocial, and environmental factors. We make recommendations to address these factors in order to improve detection, management, and prevention of suicide risk in prisoners. PMID:27278569

Stored Radioactive Material Landfill Site no. 7 (LF-7), Massachusetts Military Reservation, Cape Cod, MA

DTIC Science & Technology

2013-03-07

Consultative Letter 3. DATES COVERED (From – To) July 2012 – January 2013 4. TITLE AND SUBTITLE Stored Radioactive Material Landfill Site #7 (LF-7...performed 9-13 Jul 2012 at the stored radioactive material landfill site (LF-7) on Camp Edwards, Massachusetts Military Reservation, Cape Cod, MA...Walkover surveillance and environmental sampling were used to characterize any radioactive material presence at the LF-7 site. No observable or

UNC-1 regulates gap junctions important to locomotion in C. elegans.

PubMed

Chen, Bojun; Liu, Qiang; Ge, Qian; Xie, Jia; Wang, Zhao-Wen

2007-08-07

In C. elegans, loss-of-function (lf) mutations of the stomatin-like protein (SLP) UNC-1 and the innexin UNC-9 inhibit locomotion [1, 2] and modulate sensitivity to volatile anesthetics [3, 4]. It was unknown why unc-1(lf) and unc-9(lf) mutants have similar phenotypes. We tested the hypothesis that UNC-1 is a regulator of gap junctions formed by UNC-9. Analyses of junctional currents between body-wall muscle cells showed that electrical coupling was inhibited to a similar degree in unc-1(lf), unc-9(lf), and unc-1(lf);unc-9(lf) double mutants, suggesting that UNC-1 and UNC-9 function together. Expression of Punc-1::DsRED2 and Punc-9::GFP transcriptional fusions suggests that unc-1 and unc-9 are coexpressed in neurons and body-wall muscle cells. Immunohistochemistry showed that UNC-1 and UNC-9 colocalized at intercellular junctions and that unc-1(lf) did not alter UNC-9 expression or subcellular localization. Bimolecular fluorescence complementation (BiFC) assays suggest that UNC-1 and UNC-9 are physically very close at intercellular junctions. Targeted rescue experiments suggest that UNC-9 and UNC-1 function predominantly in neurons to control locomotion. Thus, in addition to the recently reported function of regulating mechanosensitive ion channels [5, 6], SLPs might have a novel function of regulating gap junctions.

Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin-grafted liposomes carrying quercetin

PubMed Central

Kuo, Yung-Chih; Tsao, Chien-Wei

2017-01-01

A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood–brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer’s disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils. We found that surface RMP-7 and Lf enhanced the ability of QU to cross the BBB without inducing strong toxicity and damaging the tight junction. In addition, RMP-7-Lf-QU-LS significantly reduced Aβ-induced neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU, RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier targeting the BBB to prevent Aβ-insulted neurodegeneration and may have potential in managing AD in future clinical applications. PMID:28435263

Ceruloplasmin: Macromolecular Assemblies with Iron-Containing Acute Phase Proteins

PubMed Central

Samygina, Valeriya R.; Sokolov, Alexey V.; Bourenkov, Gleb; Petoukhov, Maxim V.; Pulina, Maria O.; Zakharova, Elena T.; Vasilyev, Vadim B.; Bartunik, Hans; Svergun, Dmitri I.

2013-01-01

Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein–protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1∶1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe3+ into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

PubMed Central

Luo, Binhua; Liang, Huageng; Zhang, Shengwei; Qin, Xiaojuan; Liu, Xuhan; Liu, Wei; Zeng, Fuqing; Wu, Yun; Yang, Xiangliang

2015-01-01

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of −12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0–20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue® microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging. PMID:26396514

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging.

PubMed

Luo, Binhua; Liang, Huageng; Zhang, Shengwei; Qin, Xiaojuan; Liu, Xuhan; Liu, Wei; Zeng, Fuqing; Wu, Yun; Yang, Xiangliang

2015-01-01

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of -12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0-20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue(®) microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

Lymphatic filariasis in Peninsular Malaysia: a cross-sectional survey of the knowledge, attitudes, and practices of residents.

PubMed

Al-Abd, Nazeh M; Nor, Zurainee Mohamed; Ahmed, Abdulhamid; Al-Adhroey, Abdulelah H; Mansor, Marzida; Kassim, Mustafa

2014-11-27

Lymphatic filariasis (LF) is a major cause of permanent disability in many tropical and sub-tropical countries of the world. Malaysia is one of the countries in which LF is an endemic disease. Five rounds of the mass drug administration (MDA) program have been conducted in Malaysia as part of the Global Program to Eliminate Lymphatic Filariasis (GPELF) by year 2020. This study investigated the level of awareness of LF and the MDA program in a population living in an endemic area of the country. A descriptive cross-sectional survey that involved 230 respondents (≥15 years old) living in the LF endemic communities of Terengganu state in Peninsular Malaysia was performed. Demographic, socioeconomic, and knowledge, attitudes and practices (KAP) data of the respondents were obtained using pre-tested questionnaires and were analyzed using SPSS software version 13.0. More than 80% of the respondents were aware of LF and the common symptoms of the disease. Moreover, about 70% of the respondents that were aware of LF indicated that it is a problematic disease. Approximately 77% of the respondents indicated that filariasis is transmitted by mosquitoes. Two-thirds of respondents preferred hospital treatment for illness; however, only 12% had participated and/or received treatment for LF during an MDA program. Only 35% of the respondents that participated in this research were aware of the MDA program that had taken place in the area. None of the respondents had knowledge of the drug used in the treatment of LF. The findings from this research indicated that there was no significant association between LF awareness and with gender, age group, educational status, occupation, or socio-economic status of the respondents (P >0.05). A good proportion of the respondents are aware of LF, its mode of transmission and symptoms, however they demonstrated a poor knowledge of MDA which took place in the study area. For greater understanding of LF in the Malaysian population, there is a need for an enhancement in the delivery of health education and information programs and mass mobilization campaigns in endemic communities.

Assessing the feasibility of integration of self-care for filarial lymphoedema into existing community leprosy self-help groups in Nepal.

PubMed

Pryce, Joseph; Mableson, Hayley E; Choudhary, Ramesh; Pandey, Basu Dev; Aley, Dambar; Betts, Hannah; Mackenzie, Charles D; Kelly-Hope, Louise A; Cross, Hugh

2018-01-30

Lymphatic filariasis (LF) and leprosy are disabling infectious diseases endemic in Nepal. LF infection can lead to lymphoedema and hydrocoele, while secondary effects of leprosy infection include impairments to hands, eyes and feet. The disabling effects of both conditions can be managed through self-care and the supportive effects of self-help groups (SHGs). A network of SHGs exists for people affected by leprosy in four districts in Nepal's Central Development Region, however no such service exists for people affected by LF. The aim of this study was to determine the feasibility of integrating LF affected people into existing leprosy SHGs in this area. A survey was conducted using a semi-structured questionnaire to elicit information on: (i) participant characteristics, clinical manifestation and disease burden; (ii) participants' knowledge of management of their condition and access to services; and (iii) participants' knowledge and perceptions of the alternate condition (LF affected participants' knowledge of leprosy and vice versa) and attitudes towards integration. A total of 52 LF affected and 53 leprosy affected participants were interviewed from 14 SHGs. On average, leprosy affected participants were shown to have 1.8 times greater knowledge of self-care techniques, and practiced 2.5 times more frequently than LF affected participants. Only a quarter of LF affected participants had accessed a health service for their condition, compared with 94.3% of leprosy affected people accessing a service (including SHGs), at least once a week. High levels of stigma were perceived by both groups towards the alternate condition, however, the majority of LF (79%) and leprosy (94.3%) affected participants stated that they would consider attending an integrated SHG. LF affected participants need to increase their knowledge of self-care and access to health services. Despite stigma being a potential barrier, attitudes towards integration were positive, suggesting that the SHGs may be a good platform for LF affected people to start self-care in this area. This is not a registered trial.

Response of human limbal epithelial cells to wounding on 3D RAFT tissue equivalents: effect of airlifting and human limbal fibroblasts.

PubMed

Massie, Isobel; Levis, Hannah J; Daniels, Julie T

2014-10-01

Limbal epithelial stem cell deficiency can cause blindness but may be treated by human limbal epithelial cell (hLE) transplantation, normally on human amniotic membrane. Clinical outcomes using amnion can be unreliable and so we have developed an alternative tissue equivalent (TE), RAFT (Real Architecture for 3D Tissue), which supports hLE expansion, and stratification when airlifted. Human limbal fibroblasts (hLF) may be incorporated into RAFT TEs, where they support overlying hLE and improve phenotype. However, the impact of neither airlifting nor hLF on hLE function has been investigated. hLE on RAFT TEs (±hLF and airlifting) were wounded using heptanol and re-epithelialisation (fluorescein diacetate staining), and percentage putative stem cell marker p63α and proliferative marker Ki67 expression (wholemount immunohistochemistry), measured. Airlifted, hLF- RAFT TEs were unable to close the wound and p63α expression was 7 ± 0.2% after wounding. Conversely, non-airlifted, hLF- RAFT TEs closed the wound within 9 days and p63α expression was higher at 22 ± 5% (p < 0.01). hLE on both hLF- and hLF+ RAFT TEs (non-airlifted) closed the wound and p63α expression was 26 ± 8% and 36 ± 3% respectively (ns). Ki67 expression by hLE increased from 1.3 ± 0.5% before wounding to 7.89 ± 2.53% post-wounding for hLF- RAFT TEs (p < 0.01), and 0.8 ± 0.08% to 17.68 ± 10.88% for hLF+ RAFT TEs (p < 0.05), suggesting that re-epithelialisation was a result of proliferation. These data suggest that neither airlifting nor hLF are necessarily required to maintain a functional epithelium on RAFT TEs, thus simplifying and shortening the production process. This is important when working towards clinical application of regenerative medicine products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting

Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortlymore » after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF estimates.« less

Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti.

PubMed

Knipes, Alaine Kathryn; Lemoine, Jean Frantz; Monestime, Franck; Fayette, Carl R; Direny, Abdel N; Desir, Luccene; Beau de Rochars, Valery E; Streit, Thomas G; Renneker, Kristen; Chu, Brian K; Chang, Michelle A; Mace, Kimberly E; Won, Kimberly Y; Lammie, Patrick J

2017-02-01

Since 2001, Haiti's National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti's NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. Haiti's 2014-2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria.

Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics

NASA Astrophysics Data System (ADS)

Folkert, Michael R.; Setton, Jeremy; Apte, Aditya P.; Grkovski, Milan; Young, Robert J.; Schöder, Heiko; Thorstad, Wade L.; Lee, Nancy Y.; Deasy, Joseph O.; Oh, Jung Hun

2017-07-01

In this study, we investigate the use of imaging feature-based outcomes research (‘radiomics’) combined with machine learning techniques to develop robust predictive models for the risk of all-cause mortality (ACM), local failure (LF), and distant metastasis (DM) following definitive chemoradiation therapy (CRT). One hundred seventy four patients with stage III-IV oropharyngeal cancer (OC) treated at our institution with CRT with retrievable pre- and post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans were identified. From pre-treatment PET scans, 24 representative imaging features of FDG-avid disease regions were extracted. Using machine learning-based feature selection methods, multiparameter logistic regression models were built incorporating clinical factors and imaging features. All model building methods were tested by cross validation to avoid overfitting, and final outcome models were validated on an independent dataset from a collaborating institution. Multiparameter models were statistically significant on 5 fold cross validation with the area under the receiver operating characteristic curve (AUC)  =  0.65 (p  =  0.004), 0.73 (p  =  0.026), and 0.66 (p  =  0.015) for ACM, LF, and DM, respectively. The model for LF retained significance on the independent validation cohort with AUC  =  0.68 (p  =  0.029) whereas the models for ACM and DM did not reach statistical significance, but resulted in comparable predictive power to the 5 fold cross validation with AUC  =  0.60 (p  =  0.092) and 0.65 (p  =  0.062), respectively. In the largest study of its kind to date, predictive features including increasing metabolic tumor volume, increasing image heterogeneity, and increasing tumor surface irregularity significantly correlated to mortality, LF, and DM on 5 fold cross validation in a relatively uniform single-institution cohort. The LF model also retained significance in an independent population.

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-10-01

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competingmore » risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.« less

Mapping, Bayesian Geostatistical Analysis and Spatial Prediction of Lymphatic Filariasis Prevalence in Africa

PubMed Central

Slater, Hannah; Michael, Edwin

2013-01-01

There is increasing interest to control or eradicate the major neglected tropical diseases. Accurate modelling of the geographic distributions of parasitic infections will be crucial to this endeavour. We used 664 community level infection prevalence data collated from the published literature in conjunction with eight environmental variables, altitude and population density, and a multivariate Bayesian generalized linear spatial model that allows explicit accounting for spatial autocorrelation and incorporation of uncertainty in input data and model parameters, to construct the first spatially-explicit map describing LF prevalence distribution in Africa. We also ran the best-fit model against predictions made by the HADCM3 and CCCMA climate models for 2050 to predict the likely distributions of LF under future climate and population changes. We show that LF prevalence is strongly influenced by spatial autocorrelation between locations but is only weakly associated with environmental covariates. Infection prevalence, however, is found to be related to variations in population density. All associations with key environmental/demographic variables appear to be complex and non-linear. LF prevalence is predicted to be highly heterogenous across Africa, with high prevalences (>20%) estimated to occur primarily along coastal West and East Africa, and lowest prevalences predicted for the central part of the continent. Error maps, however, indicate a need for further surveys to overcome problems with data scarcity in the latter and other regions. Analysis of future changes in prevalence indicates that population growth rather than climate change per se will represent the dominant factor in the predicted increase/decrease and spread of LF on the continent. We indicate that these results could play an important role in aiding the development of strategies that are best able to achieve the goals of parasite elimination locally and globally in a manner that may also account for the effects of future climate change on parasitic infection. PMID:23951194

Low fat-containing elemental formula is effective for postoperative recovery and potentially useful for preventing chyle leak during postoperative early enteral nutrition after esophagectomy.

PubMed

Moro, Kazuki; Koyama, Yu; Kosugi, Shin-Ichi; Ishikawa, Takashi; Ichikawa, Hiroshi; Hanyu, Takaaki; Miura, Kohei; Nagahashi, Masayuki; Nakajima, Masato; Tatsuda, Kumiko; Tsuchida, Junko; Toshikawa, Chie; Ikarashi, Mayuko; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Kameyama, Hitoshi; Wakai, Toshifumi

2016-12-01

Transthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery. A total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak. Patients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P < 0.01). Duration of respirator use and length of ICU stay were also significantly shorter, and TPN was used significantly less in Group LF compared to Group F (P < 0.05). Postoperative chyle leak was observed in six patients in total (8.1%); five patients in Group F and one patient in Group LF, although there was no significant difference in frequency of chyle leak per patient between Group LF and Group F. Early EN using low-fat elemental formula after esophagectomy with three-field lymphadenectomy was safe and valid for postoperative recovery and potentially useful in preventing chyle leak. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women.

PubMed

Meckling, Kelly A; O'Sullivan, Caitriona; Saari, Dayna

2004-06-01

Overweight and obese men and women (24-61 yr of age) were recruited into a randomized trial to compare the effects of a low-fat (LF) vs. a low-carbohydrate (LC) diet on weight loss. Thirty-one subjects completed all 10 wk of the diet intervention (retention, 78%). Subjects on the LF diet consumed an average of 17.8% of energy from fat, compared with their habitual intake of 36.4%, and had a resulting energy restriction of 2540 kJ/d. Subjects on the LC diet consumed an average of 15.4% carbohydrate, compared with habitual intakes of about 50% carbohydrate, and had a resulting energy restriction of 3195 kJ/d. Both groups of subjects had significant weight loss over the 10 wk of diet intervention and nearly identical improvements in body weight and fat mass. LF subjects lost an average of 6.8 kg and had a decrease in body mass index of 2.2 kg/m2, compared with a loss of 7.0 kg and decrease in body mass index of 2.1 kg/m2 in the LC subjects. The LF group better preserved lean body mass when compared with the LC group; however, only the LC group had a significant decrease in circulating insulin concentrations. Group results indicated that the diets were equally effective in reducing systolic blood pressure by about 10 mm Hg and diastolic pressure by 5 mm Hg and decreasing plasminogen activator inhibitor-1 bioactivity. Blood beta-hydroxybutyrate concentrations were increased in the LC only, at the 2- and 4-wk time points. These data suggest that energy restriction achieved by a very LC diet is equally effective as a LF diet strategy for weight loss and decreasing body fat in overweight and obese adults.

Lactoferrin-derived resistance against plant pathogens in transgenic plants.

PubMed

Lakshman, Dilip K; Natarajan, Savithiry; Mandal, Sudhamoy; Mitra, Amitava

2013-12-04

Lactoferrin (LF) is a ubiquitous cationic iron-binding milk glycoprotein that contributes to nutrition and exerts a broad-spectrum primary defense against bacteria, fungi, protozoa, and viruses in mammals. These qualities make lactoferrin protein and its antimicrobial motifs highly desirable candidates to be incorporated in plants to impart broad-based resistance against plant pathogens or to economically produce them in bulk quantities for pharmaceutical and nutritional purposes. This study introduced bovine LF (BLF) gene into tobacco ( Nicotiana tabacum var. Xanthi), Arabidopsis ( A. thaliana ) and wheat ( Triticum aestivum ) via Agrobacterium -mediated plant transformation. Transgenic plants or detached leaves exhibited high levels of resistance against the damping-off causing fungal pathogen Rhizoctonia solani and the head blight causing fungal pathogen Fusarium graminearum . LF also imparted resistance to tomato plants against a bacterial pathogen, Ralstonia solanacearum . Similarly, other researchers demonstrated expression of LF and LF-mediated high-quality resistance to several other aggressive fungal and bacterial plant pathogens in transgenic plants and against viral pathogens by foliar applications of LF or its derivatives. Taken together, these studies demonstrated the effectiveness of LF for improving crop quality and its biopharming potentials for pharmaceautical and nutritional applications.

Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle.

PubMed

Huang, J M; Wang, Z Y; Ju, Z H; Wang, C F; Li, Q L; Sun, T; Hou, Q L; Hang, S Q; Hou, M H; Zhong, J F

2011-12-21

Bovine lactoferrin (bLF) is a member of the transferrin family; it plays an important role in the innate immune response. We identified novel splice variants of the bLF gene in mastitis-infected and healthy cows. Reverse transcription-polymerase chain reaction (RT-PCR) and clone sequencing analysis were used to screen the splice variants of the bLF gene in the mammary gland, spleen and liver tissues. One main transcript corresponding to the bLF reference sequence was found in three tissues in both healthy and mastitis-infected cows. Quantitative real-time PCR analysis showed that the expression levels of the LF gene's main transcript were not significantly different in tissues from healthy versus mastitis-infected cows. However, the new splice variant, LF-AS2, which has the exon-skipping alternative splicing pattern, was only identified in mammary glands infected with Staphylococcus aureus. Sequencing analysis showed that the new splice variant was 251 bp in length, including exon 1, part of exon 2, part of exon 16, and exon 17. We conclude that bLF may play a role in resistance to mastitis through alternative splicing mechanisms.

Inhibition of HSV cell-to-cell spread by lactoferrin and lactoferricin.

PubMed

Jenssen, Håvard; Sandvik, Kjersti; Andersen, Jeanette H; Hancock, Robert E W; Gutteberg, Tore J

2008-09-01

The milk protein lactoferrin (Lf) has multiple functions, including immune stimulation and antiviral activity towards herpes simplex virus 1 and 2 (HSV-1 and HSV-2); antiviral activity has also been reported for the N-terminal pepsin-derived fragment lactoferricin (Lfcin). The anti-HSV mode of action of Lf and Lfcin is assumed to involve, in part, their interaction with the cell surface glycosaminoglycan heparan sulfate, thereby blocking of viral entry. In this study we investigated the ability of human and bovine Lf and Lfcin to inhibit viral cell-to-cell spread as well as the involvement of cell surface glycosaminoglycans during viral cell-to-cell spread. Lf and Lfcin from both human and bovine origin, inhibited cell-to-cell spread of both HSV-1 and HSV-2. Inhibition of cell-to-cell spread by bovine Lfcin involved cell surface chondroitin sulfate. Based on transmission electron microscopy studies, human Lfcin, like bovine Lfcin, was randomly distributed intracellularly, thus differences in their antiviral activity could not be explained by differences in their distribution. In contrast, the cellular localization of iron-saturated (holo)-Lf appeared to differ from that of apo-Lf, indicating that holo- and apo-Lf may exhibit different antiviral mechanisms.

Apoptotic effects of bovine apo-lactoferrin on HeLa tumor cells.

PubMed

Luzi, Carla; Brisdelli, Fabrizia; Iorio, Roberto; Bozzi, Argante; Carnicelli, Veronica; Di Giulio, Antonio; Lizzi, Anna Rita

2017-01-01

Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD + . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH depletion. On the whole, apo-bLf triggered apoptosis of HeLa cells upon oxygen radicals burst and GSH decrease. Copyright © 2017 John Wiley & Sons, Ltd.

Low-fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women.

PubMed

Young, Lindsay R; Kurzer, Mindy S; Thomas, William; Redmon, J Bruce; Raatz, Susan K

2013-07-01

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in healthy individuals are not well defined. Three test diets-high-fat diet (40% energy as fat), low-fat diet (LF; 20% energy as fat), and a diet with low fat and high omega-3 fatty acid (LFn3; 23% energy as fat)--were tested in a randomized crossover designed controlled feeding trial in healthy postmenopausal women. Plasma IGF-I, IGF binding protein-3 (IGFBP-3), insulin, glucose, and ratio of IGF-I/IGFBP-3 concentrations were measured in response to diets. Insulin sensitivity was calculated using the homeostatic model assessment of insulin resistance We hypothesized that IGF-I, insulin, and glucose concentrations would decrease and IGFBP-3 concentration would increase in response to the low-fat diets. Eight weeks of the LFn3 diet increased circulating IGF-I (P < .001) and IGFBP-3 (P = .01) and the LF diet increased IGFBP-3 (P = .04), resulting in trends toward an increased IGF-I/IGFBP-3 ratio with the LFn3 diet and a decreased IGF-I/IGFBP-3 ratio with the LF diet (P = .13 for both comparisons). No statistically significant differences were detected between treatments at baseline or 8 weeks for IGF-1, IGFBP-3, or the ratio of IGF-1/IGFBP-3. Insulin, glucose, and the homeostatic model assessment of insulin resistance were not altered by the interventions. Low-fat diet with high n-3 fatty acids may increase circulating IGF-I concentrations without adversely affecting insulin sensitivity in healthy individuals. Published by Elsevier Inc.

Global transcriptome analysis of the maize (Zea mays L.) inbred line 08LF during leaf senescence initiated by pollination-prevention

PubMed Central

Wang, Shunxi; Wu, Liuji; Ku, Lixia; Zhang, Jun; Song, Xiaoheng; Liu, Haiping

2017-01-01

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention. PMID:28973044

Novel recombinant human lactoferrin: differential activation of oxidative stress related gene expression.

PubMed

Kruzel, Marian L; Actor, Jeffrey K; Zimecki, Michał; Wise, Jasen; Płoszaj, Paulina; Mirza, Shaper; Kruzel, Mark; Hwang, Shen-An; Ba, Xueqing; Boldogh, Istvan

2013-12-01

Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. The aim of this study was to scale-up expression and purification of rhLF in a CHO expression system, verify its glycan primary structure, and assess its biological properties in cell culture models. A stable CHO cell line producing >200mg/L of rhLF was developed and established. rhLF was purified by a single-step cation-exchange chromatography procedure. The highly homogenous rhLF has a molecular weight of approximately 80 kDa. MALDI-TOF mass spectrometric analysis revealed N-linked, partially sialylated glycans at two glycosylation sites, typical for human milk LF. This novel rhLF showed a protective effect against oxidative stress in a similar manner to its natural counterpart. In addition, rhLF revealed a modulatory effect on cellular redox via upregulation of key antioxidant enzymes. These data imply that the CHO-derived rhLF is fully compatible with the native molecule, thus it has promise for human therapeutic applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Multicentre evaluations of two new rapid IgG4 tests (WB rapid and panLF rapid) for detection of lymphatic filariasis

PubMed Central

Noordin, Rahmah; Itoh, Makoto; Kimura, Eisaku; Abdul Rahman, Rohana; Ravindran, Balachandran; Mahmud, Rohela; Supali, Taniawati; Weerasooriya, Mirani

2007-01-01

In the global effort to eliminate lymphatic filariasis (LF), rapid field-applicable tests are useful tools that will allow on-site testing to be performed in remote places and the results to be obtained rapidly. Exclusive reliance on the few existing tests may jeopardize the progress of the LF elimination program, thus the introduction of other rapid tests would be useful to address this issue. Two new rapid immunochromatographic IgG4 cassette tests have been produced, namely WB rapid and panLF rapid, for detection of bancroftian filariasis and all three species of lymphatic filaria respectively. WB rapid was developed using BmSXP recombinant antigen, while PanLF rapid was developed using BmR1 and BmSXP recombinant antigens. A total of 165 WB rapid and 276 panLF rapid tests respectively were evaluated at USM and the rest were couriered to another university in Malaysia (98 WB rapid, 129 panLF rapid) and to universities in Indonesia (56 WB rapid, 62 panLF rapid), Japan (152 of each test) and India (18 of each test) where each of the tests underwent independent evaluations in a blinded manner. The average sensitivities of WB rapid and panLF rapid were found to be 97.6% (94%–100%) and 96.5% (94%–100%) respectively; while their average specificities were both 99.6% (99%–100%). Thus this study demonstrated that both the IgG4 rapid tests were highly sensitive and specific, and would be useful additional tests to facilitate the global drive to eliminate this disease. PMID:17961262

Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers

PubMed Central

Kamalapuram, Sishir K; Kanwar, Rupinder K; Roy, Kislay; Chaudhary, Rajneesh; Sehgal, Rakesh; Kanwar, Jagat R

2016-01-01

The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1+/CIMP2−/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER−/PR−/HER2−; MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm3, and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm3. In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm3 within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy. PMID:27099495

Effects of the major sudden stratospheric warming event of 2009 on the subionospheric very low frequency/low frequency radio signals

NASA Astrophysics Data System (ADS)

Pal, S.; Hobara, Y.; Chakrabarti, S. K.; Schnoor, P. W.

2017-07-01

This paper presents effects of the major sudden stratospheric warming (SSW) event of 2009 on the subionospheric very low frequency/low frequency (VLF/LF) radio signals propagating in the Earth-ionosphere waveguide. Signal amplitudes from four transmitters received by VLF/LF radio networks of Germany and Japan corresponding to the major SSW event are investigated for possible anomalies and atmospheric influence on the high- to middle-latitude ionosphere. Significant anomalous increase or decrease of nighttime and daytime amplitudes of VLF/LF signals by ˜3-5 dB during the SSW event have been found for all propagation paths associated with stratospheric temperature rise at 10 hPa level. Increase or decrease in VLF/LF amplitudes during daytime and nighttime is actually due to the modification of the lower ionospheric boundary conditions in terms of electron density and electron-neutral collision frequency profiles and associated modal interference effects between the different propagating waveguide modes during the SSW period. TIMED/SABER mission data are also used to investigate the upper mesospheric conditions over the VLF/LF propagation path during the same time period. We observe a decrease in neutral temperature and an increase in pressure at the height of 75-80 km around the peak time of the event. VLF/LF anomalies are correlated and in phase with the stratospheric temperature and mesospheric pressure variation, while minimum of mesospheric cooling shows a 2-3 day delay with maximum VLF/LF anomalies. Simulations of VLF/LF diurnal variation are performed using the well-known Long Wave Propagating Capability (LWPC) code within the Earth-ionosphere waveguide to explain the VLF/LF anomalies qualitatively.

Inhibition of Hyphal Growth of Azole-Resistant Strains of Candida albicans by Triazole Antifungal Agents in the Presence of Lactoferrin-Related Compounds

PubMed Central

Wakabayashi, Hiroyuki; Abe, Shigeru; Teraguchi, Susumu; Hayasawa, Hirotoshi; Yamaguchi, Hideyo

1998-01-01

The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide lactoferricin B (LFcin B) on the growth of Candida albicans hyphae, including those of three azole-resistant strains, were investigated by a crystal violet staining method. The hyphae of two highly azole-resistant strains were more susceptible to inhibition by LF or LFcin B than the azole-susceptible strains tested. One moderately azole-resistant strain was defective in the formation of hyphae and showed a susceptibility to LF greater than that of the susceptible strains but a susceptibility to LFcin B similar to that of the susceptible strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the presence of fluconazole or itraconazole, while the extent of growth was reduced by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole for TIMM3317 was shifted from >256 to 0.25 μg/ml by LF, but the MICs were not decreased for the susceptible strains. The combination effects observed with triazoles and LF-related compounds in the case of the two highly azole-resistant strains were confirmed to be synergistic by the fractional inhibitory concentration index. These results demonstrate that for some azole-resistant C. albicans strains, LF-related compounds combined with triazoles can inhibit the growth of hyphae, an important form of this organism in pathogenesis. PMID:9660988

Production of human lactoferrin in animal milk.

PubMed

Goldman, I L; Georgieva, S G; Gurskiy, Ya G; Krasnov, A N; Deykin, A V; Popov, A N; Ermolkevich, T G; Budzevich, A I; Chernousov, A D; Sadchikova, E R

2012-06-01

Genetic constructs containing the human lactoferrin (hLf) gene were created within a joint program of Russian and Belorussian scientists. Using these constructs, transgenic mice were bred (the maximum hLf concentration in their milk was 160 g/L), and transgenic goats were also generated (up to 10 g/L hLf in their milk). Experimental goatherds that produced hLf in their milk were also bred, and the recombinant hLf was found to be identical to the natural protein in its physical and chemical properties. These properties included electrophoretic mobility, isoelectric point, recognition by polyclonal and monoclonal antibodies, circular dichroic spectra, interaction with natural ligands (DNA, lipopolysaccharides, and heparin), the binding of iron ions, the sequence of the 7 terminal amino acids, and its biological activity. The latter was assessed by the agglutination of Micrococcus luteus protoplasts, bactericidal activity against Escherichia coli and Listeria monocytogenes , and fungicidal activity against Candida albicans . We also demonstrated a significant increase in the activity of antibiotics when used in combination with Lf.

Implantable Cardiac Defibrillator Lead Failure and Management.

PubMed

Swerdlow, Charles D; Kalahasty, Gautham; Ellenbogen, Kenneth A

2016-03-22

The implantable-cardioverter defibrillator (ICD) lead is the most vulnerable component of the ICD system. Despite advanced engineering design, sophisticated manufacturing techniques, and extensive bench, pre-clinical, and clinical testing, lead failure (LF) remains the Achilles' heel of the ICD system. ICD LF has a broad range of adverse outcomes, ranging from intermittent inappropriate pacing to proarrhythmia leading to patient mortality. ICD LF is often considered in the context of design or construction defects, but is more appropriately considered in the context of the finite service life of a mechanical component placed in chemically stressful environment and subjected to continuous mechanical stresses. This clinical review summarizes LF mechanisms, assessment, and differential diagnosis of LF, including lead diagnostics, recent prominent lead recalls, and management of LF and functioning, but recalled leads. Despite recent advances in lead technology, physicians will likely continue to need to understand how to manage patients with transvenous ICD leads. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Systematic Evaluation of Low-Frequency Hiss and Energetic Electron Injections

DOE PAGES

Shi, Run; Li, Wen; Ma, Qianli; ...

2017-10-05

Here, the excitation of low-frequency (LF) plasmaspheric hiss, over the frequency range from 20 Hz to 100 Hz, is systematically investigated by comparing the hiss wave properties with electron injections at energies from tens of keV to several hundreds of keV. Both particle and wave data from the Van Allen Probes during the period from September 2012 to June 2016 are used in the present study. Our results demonstrate that the intensity of LF hiss has a clear day-night asymmetry, and increases with increasing geomagnetic activity, similar to the behavior of normal hiss (approximately hundred of hertz to several kilohertz).more » The occurrence rate of LF hiss in association with electron injections is up to 80% in the outer plasmasphere ( L > 4) on the dayside, and the strong correlation extends to lower L shells for more active times. In contrast, at lower L shells ( L < 3.5), LF hiss is seldom associated with electron injections. The LF hiss with Poynting flux directed away from the equator is dominant at higher magnetic latitudes and higher L shells, suggesting a local amplification of LF hiss in the outer plasmasphere. The averaged electron fluxes are larger at higher L shells, where significant LF hiss wave events are observed. Our study suggests the importance of electron injections and their drift trajectories toward the dayside plasmasphere in locally amplifying the LF hiss waves detected by the Van Allen Probes.« less

Systematic Evaluation of Low-Frequency Hiss and Energetic Electron Injections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Run; Li, Wen; Ma, Qianli

Here, the excitation of low-frequency (LF) plasmaspheric hiss, over the frequency range from 20 Hz to 100 Hz, is systematically investigated by comparing the hiss wave properties with electron injections at energies from tens of keV to several hundreds of keV. Both particle and wave data from the Van Allen Probes during the period from September 2012 to June 2016 are used in the present study. Our results demonstrate that the intensity of LF hiss has a clear day-night asymmetry, and increases with increasing geomagnetic activity, similar to the behavior of normal hiss (approximately hundred of hertz to several kilohertz).more » The occurrence rate of LF hiss in association with electron injections is up to 80% in the outer plasmasphere ( L > 4) on the dayside, and the strong correlation extends to lower L shells for more active times. In contrast, at lower L shells ( L < 3.5), LF hiss is seldom associated with electron injections. The LF hiss with Poynting flux directed away from the equator is dominant at higher magnetic latitudes and higher L shells, suggesting a local amplification of LF hiss in the outer plasmasphere. The averaged electron fluxes are larger at higher L shells, where significant LF hiss wave events are observed. Our study suggests the importance of electron injections and their drift trajectories toward the dayside plasmasphere in locally amplifying the LF hiss waves detected by the Van Allen Probes.« less

Release of endogenous opioids following transcutaneous electric nerve stimulation in an experimental model of acute inflammatory pain.

PubMed

Sabino, George S; Santos, Cristiane M F; Francischi, Janetti N; de Resende, Marcos Antônio

2008-02-01

Transcutaneous electric nerve stimulation (TENS) is a noninvasive treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. The aim of the present study was to investigate the action mechanism of TENS at high (HF: 130 Hz) and low (LF: 10 Hz) frequencies in an inflammation model produced by the injection of carrageenan in rat paws (Cg; 250 microg). After carrageenan administration (0 time), either HF or LF TENS was applied to the inflamed paw of rats for 20 minutes, and hyperalgesia was assessed hourly using the modified Randall-Selitto method (1957). HF and LF TENS inhibited the carrageenan-induced hyperalgesia by 100%. Pretreatment of animals with intraplantar naltrexone (Nx; 50 microg) reversed the analgesic effect of the LF TENS but did not alter the effect of HF TENS. The application of HF and LF TENS to the contralateral paw reversed the hyperalgesia of the inflamed paw similar to that observed when TENS was applied to the inflamed paw. However, LF TENS presented a longer-lasting analgesic effect than HF TENS. Our data demonstrate that HF and LF TENS induced antihyperalgesia. We also report that the antihyperalgesia provoked by LF TENS is partially due to the local release of endogenous opioids. This study offers important information about physiotherapy practices aimed at pain relieving. TENS is a noninvasive treatment that promotes analgesia in acute and chronic inflammatory conditions. Scientists, patients, and the general population may benefit from this knowledge.

Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection.

PubMed

Cieslak, Kasia P; Bennink, Roelof J; de Graaf, Wilmar; van Lienden, Krijn P; Besselink, Marc G; Busch, Olivier R C; Gouma, Dirk J; van Gulik, Thomas M

2016-09-01

(99m)Tc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated. 163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m(2) were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods. 29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods. Implementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Lactoferrin binding protein B – a bi-functional bacterial receptor protein

PubMed Central

Ostan, Nicholas K. H.; Yu, Rong-Hua; Ng, Dixon; Lai, Christine Chieh-Lin; Sarpe, Vladimir; Schriemer, David C.

2017-01-01

Lactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated that LbpB plays a role in protecting the bacteria from cationic antimicrobial peptides due to large regions rich in anionic residues in the C-terminal lobe. Relative to its homolog, transferrin-binding protein B (TbpB), there currently is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. In this study, a combination of crosslinking and deuterium exchange coupled to mass spectrometry, information-driven computational docking, bio-layer interferometry, and site-directed mutagenesis was used to probe LbpB:hLf complexes. The formation of a 1:1 complex of iron-loaded Lf and LbpB involves an interaction between the Lf C-lobe and LbpB N-lobe, comparable to TbpB, consistent with a potential role in iron acquisition. The Lf N-lobe is also capable of binding to negatively charged regions of the LbpB C-lobe and possibly other sites such that a variety of higher order complexes are formed. Our results are consistent with LbpB serving dual roles focused primarily on iron acquisition when exposed to limited levels of iron-loaded Lf on the mucosal surface and effectively binding apo Lf when exposed to high levels at sites of inflammation. PMID:28257520

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

PubMed Central

Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Introduction Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Conclusion Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD. PMID:29391788

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects.

PubMed

Yan, Xiuju; Xu, Lixiao; Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference ( P <0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.

The rubber plantation environment and Lassa fever epidemics in Liberia, 2008-2012: a spatial regression.

PubMed

Olugasa, Babasola O; Dogba, John B; Ogunro, Bamidele; Odigie, Eugene A; Nykoi, Jomah; Ojo, Johnson F; Taiwo, Olalekan; Kamara, Abraham; Mulbah, Charles K; Fasunla, Ayotunde J

2014-10-01

As Lassa fever continues to be a public health challenge in West Africa, it is critical to produce good maps of its risk pattern for use in active surveillance and control intervention. We identified eight spatial features related to the rubber plantation environment and used them as explanatory variables for Lassa fever (LF) outbreaks on the Uniroyal Liberian Agricultural Company (LAC) rubber plantation environment in Grand Bassa County, Liberia. We computed classical and spatial lag regression models on all spatial features, including proximity of residential camp to rubber tree-edge, main road in the plantation, LAC hospital, rice farmland, household refuse dump, human population density, post-harvest storage density of rice and density of rodent deterrent on rice storage. We found significant (p=0.0024) spatial autocorrelation between LF cases and the spatial features we have considered. We concluded that the rubber plantation environment influenced Mastomys species' breeding and transmission of Lassa virus along spatial scale to humans. The risk factors identified in this study offered a baseline for more effective surveillance and control of LF in the post-civil conflict Liberia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ectopic fat is linked to prior cardiovascular events in men with HIV.

PubMed

Orlando, Gabriella; Gabriella, Orlando; Guaraldi, Giovanni; Giovanni, Guaraldi; Zona, Stefano; Stefano, Zona; Carli, Federica; Federica, Carli; Bagni, Pietro; Pietro, Bagni; Menozzi, Marianna; Marianna, Menozzi; Cocchi, Stefania; Stefania, Cocchi; Scaglioni, Riccardo; Riccardo, Scaglioni; Ligabue, Guido; Guido, Ligabue; Raggi, Paolo; Paolo, Raggi

2012-04-15

Epicardial Adipose Tissue (EAT) has been associated with adverse cardiovascular events in the general population. We studied the association of general adiposity measures (body mass index, waist circumference) and ectopic adipose tissue [visceral adipose tissue (VAT); liver fat (LF); EAT) with prevalent cardiovascular disease (CVD) (prior myocardial infarction, coronary revascularization, stroke, peripheral vascular disease] in 583 HIV-infected men. VAT, EAT, and LF (liver/spleen attenuation ratio < 1.1) were measured by computed tomography. Patients' mean age was 48.5 ± 8.1 years, prior CVD was present in 33 (5.7%) patients. Factors independently associated with CVD on multivariable analyses were age [incidence-rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.02 to 1.12], smoking (IRR = 2.70, 95% CI: 1.22 to 6.01), Center for Disease Control group C (IRR = 3.09, 95% CI: 1.41 to 6.76), EAT (IRR = 1.13, 95% CI: 1.04 to 1.24, per 10 cm), LF (IRR = 1.17, 95% CI: 1.04 to 1.32), and VAT (IRR = 1.05, 95% CI: 1.00 to 1.10, per 10 cm). Ectopic fat but not general adiposity measures were associated with prevalent CVD in men with HIV.

Distal scar-to-midline distance in pilonidal Limberg flap surgery is a recurrence-promoting factor: A multicenter, case-control study.

PubMed

Kaplan, Mehmet; Ozcan, Onder; Bilgic, Ethem; Kaplan, Elif Tugce; Kaplan, Tugba; Kaplan, Fatma Cigdem

2017-11-01

The Limberg flap (LF) procedure is widely performed for the treatment of sacrococcygeal pilonidal sinus (SPS); however, recurrences continues to be observed. The aim of this study was to assess the relationship between LF designs and the risk of SPS recurrence. Sixty-one cases with recurrent disease (study group) and 194 controls, with a minimum of 5 recurrence-free years following surgery (control group), were included in the study. LF reconstructions performed in each group were classified as off-midline closure (OMC) and non-OMC types. Subsequently, the 2 groups were analyzed. After adjustment for all variables, non-OMC types showed the most prominent correlation with recurrence, followed by interrupted suturing type, family history of SPS, smoking, prolonged healing time, and younger age. The best cut-off value for the critical distance from the midline was found to be 11 mm (with 72% sensitivity and 95% specificity for recurrence). We recommend OMC modifications, with the flap tailored to create a safe margin of at least 2 cm between the flap borders and the midline. Copyright © 2017 Elsevier Inc. All rights reserved.

Lassa Fever Immune Plasma.

DTIC Science & Technology

1984-08-01

three instances, and one each for sickle cell crisis , severe anemia, pyelonephritis, cerebral malaria and tonsillitis. Treatment of LF with LFIP under...diagnosis of 46 LF and Presumptive LF patients treated at CLH April 1983 - March 1984. Clinical diagnosis No. Lassa fever 38 Typhoid fever 3 Sickle cell crisis 1

Effect of the glycemic index of the diet on weight loss, modulation of satiety, inflammation, and other metabolic risk factors: a randomized controlled trial.

PubMed

Juanola-Falgarona, Martí; Salas-Salvadó, Jordi; Ibarrola-Jurado, Núria; Rabassa-Soler, Antoni; Díaz-López, Andrés; Guasch-Ferré, Marta; Hernández-Alonso, Pablo; Balanza, Rafael; Bulló, Mònica

2014-07-01

Low-glycemic index (GI) diets have been proven to have beneficial effects in such chronic conditions as type 2 diabetes, ischemic heart disease, and some types of cancer, but the effect of low-GI diets on weight loss, satiety, and inflammation is still controversial. We assessed the efficacy of 2 moderate-carbohydrate diets and a low-fat diet with different GIs on weight loss and the modulation of satiety, inflammation, and other metabolic risk markers. The GLYNDIET study is a 6-mo randomized, parallel, controlled clinical trial conducted in 122 overweight and obese adults. Participants were randomly assigned to one of the following 3 isocaloric energy-restricted diets for 6 mo: 1) a moderate-carbohydrate and high-GI diet (HGI), 2) a moderate-carbohydrate and low-GI diet (LGI), and 3) a low-fat and high-GI diet (LF). At weeks 16 and 20 and the end of the intervention, changes in body mass index (BMI; in kg/m(2)) differed significantly between intervention groups. Reductions in BMI were greater in the LGI group than in the LF group, whereas in the HGI group, reductions in BMI did not differ significantly from those in the other 2 groups (LGI: -2.45 ± 0.27; HGI: -2.30 ± 0.27; LF: -1.43 ± 0.27; F = 4.616, P = 0.012; pairwise comparisons: LGI compared with HGI, P = 1.000; LGI compared with LF, P = 0.016; HGI compared with LF, P = 0.061). The decrease in fasting insulin, homeostatic model assessment of insulin resistance, and homeostatic model assessment of β cell function was also significantly greater in the LGI group than in the LF group (P < 0.05). Despite this tendency for a greater improvement with a low-GI diet, the 3 intervention groups were not observed to have different effects on hunger, satiety, lipid profiles, or other inflammatory and metabolic risk markers. A low-GI and energy-restricted diet containing moderate amounts of carbohydrates may be more effective than a high-GI and low-fat diet at reducing body weight and controlling glucose and insulin metabolism. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN54971867. © 2014 American Society for Nutrition.

Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial1234

PubMed Central

Jebb, Susan A; Lovegrove, Julie A; Griffin, Bruce A; Frost, Gary S; Moore, Carmel S; Chatfield, Mark D; Bluck, Les J; Williams, Christine M; Sanders, Thomas AB

2010-01-01

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain. Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome. Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets. Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10−4 mL · μU−1 · min−1 (interquartile range: 2.0, 4.2 × 10−4 mL · μU−1 · min−1), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, −4% (−12.7%, 5.3%); for the HM/HGI group, 2.1% (−5.8%, 10.7%); for the HM/LGI group, −3.5% (−10.6%, 4.3%); for the LF/HGI group, −8.6% (−15.4%, −1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations. Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298. PMID:20739418

THE LUMINOSITY FUNCTION OF FERMI-DETECTED FLAT-SPECTRUM RADIO QUASARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajello, M.; Shaw, M. S.; Romani, R. W.

2012-06-01

Fermi has provided the largest sample of {gamma}-ray-selected blazars to date. In this work we use a complete sample of flat spectrum radio quasars (FSRQs) detected during the first year of operation to determine the luminosity function (LF) and its evolution with cosmic time. The number density of FSRQs grows dramatically up to redshift {approx}0.5-2.0 and declines thereafter. The redshift of the peak in the density is luminosity dependent, with more luminous sources peaking at earlier times; thus the LF of {gamma}-ray FSRQs follows a luminosity-dependent density evolution similar to that of radio-quiet active galactic nuclei. Also, using data frommore » the Swift Burst Alert Telescope we derive the average spectral energy distribution (SED) of FSRQs in the 10 keV-300 GeV band and show that there is no correlation between the luminosity at the peak of the {gamma}-ray emission component and its peak frequency. Using this luminosity-independent SED with the derived LF allows us to predict that the contribution of FSRQs to the Fermi isotropic {gamma}-ray background is 9.3{sup +1.6}{sub -1.0}% ({+-}3% systematic uncertainty) in the 0.1-100 GeV band. Finally we determine the LF of unbeamed FSRQs, finding that FSRQs have an average Lorentz factor of {gamma} = 11.7{sup +3.3}{sub -2.2}, that most are seen within 5 Degree-Sign of the jet axis, and that they represent only {approx}0.1% of the parent population.« less

Heart rate variability and implication for sport concussion.

PubMed

Bishop, Scott A; Dech, Ryan T; Guzik, Przemyslaw; Neary, J Patrick

2017-11-16

Finding sensitive and specific markers for sports-related concussion is both challenging and clinically important. Such biomarkers might be helpful in the management of patients with concussion (i.e. diagnosis, monitoring and risk prediction). Among many parameters, blood flow-pressure metrics and heart rate variability (HRV) have been used to gauge concussion outcomes. Reports on the relation between HRV and both acute and prolonged concussion recovery are conflicting. While some authors report on differences in the low-frequency (LF) component of HRV during postural manipulations and postexercise conditions, others observe no significant differences in various HRV measures. Despite the early success of using the HRV LF for concussion recovery, the interpretation of the LF is debated. Recent research suggests the LF power is a net effect of several intrinsic modulatory factors from both sympathetic and parasympathetic branches of the autonomic nervous system, vagally mediated baroreflex and even some respiratory influences at lower respiratory rate. There are only a few well-controlled concussion studies that specifically examine the contribution of the autonomic nervous system branches with HRV for concussion management. This study reviews the most recent HRV- concussion literature and the underlying HRV physiology. It also highlights cerebral blood flow studies related to concussion and the importance of multimodal assessment of various biological signals. It is hoped that a better understanding of the physiology behind HRV might generate cost-effective, repeatable and reliable protocols, all of which will improve the interpretation of HRV throughout concussion recovery. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

[A clinical study on the relationship of autonomic nervous function and arteriosclerosis in patients with essential hypertension].

PubMed

Zhao, G; Li, S H; Tan, X

2016-03-01

To investigate the relationship between autonomic nervous function and arteriosclerosis in patients with essential hypertension. From January 2011 to December 2013, a total of 269 patients with essential hypertension hospitalized in Chang'an Branch of First People's Hospital of Liangshan were divided into normal PWV group (PWV<9 m/s, n=178) and high PWV group (PWV≥9 m/s, n=91) via the results of carotid-femoral pulse wave velocity (PWV). Synchronic 24 hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed for all participants to simultaneously monitor the heart rate variability (HRV) and blood pressure variability (BPV) in these patients. Pearson single factor analysis and multivariate logistic regression analysis were performed to define the relationship between PWV and HRV, BPV respectively. The level of nHR/dHR (index of heart rate variability), 24 hour'sSSD, dSSD, nSSD (indexes of blood pressure variability) increased significantly (all P<0.05), while the level of SDANN (index of heart rate variability) decreased significantly (P<0.05) in high PWV group compared with normal PWV group. Multiple linear regression analysis showed that PWV was positively correlated with 24 hour'sSSD, 24 hour'sPP, LF, LF/HF and night/day heart rate ratio (all P<0.05). HRV (LF, LF/HF, nHR/dHR) and BPV (24 hours'SSD, dSSD, nSSD) are positively correlated to arteriosclerosis in patients with essential hypertension. Our results show that sympathetic activation and vascular injury are closely related in patients with essential hypertension.

A Review of Factors That Influence Individual Compliance with Mass Drug Administration for Elimination of Lymphatic Filariasis

PubMed Central

Krentel, Alison; Fischer, Peter U.; Weil, Gary J.

2013-01-01

Background The success of programs to eliminate lymphatic filariasis (LF) depends in large part on their ability to achieve and sustain high levels of compliance with mass drug administration (MDA). This paper reports results from a comprehensive review of factors that affect compliance with MDA. Methodology/Principal Findings Papers published between 2000 and 2012 were considered, and 79 publications were included in the final dataset for analysis after two rounds of selection. While results varied in different settings, some common features were associated with successful programs and with compliance by individuals. Training and motivation of drug distributors is critically important, because these people directly interact with target populations, and their actions can affect MDA compliance decisions by families and individuals. Other important programmatic issues include thorough preparation of personnel, supplies, and logistics for implementation and preparation of the population for MDA. Demographic factors (age, sex, income level, and area of residence) are often associated with compliance by individuals, but compliance decisions are also affected by perceptions of the potential benefits of participation versus the risk of adverse events. Trust and information can sometimes offset fear of the unknown. While no single formula can ensure success MDA in all settings, five key ingredients were identified: engender trust, tailor programs to local conditions, take actions to minimize the impact of adverse events, promote the broader benefits of the MDA program, and directly address the issue of systematic non-compliance, which harms communities by prolonging their exposure to LF. Conclusions/Significance This review has identified factors that promote coverage and compliance with MDA for LF elimination across countries. This information may be helpful for explaining results that do not meet expectations and for developing remedies for ailing MDA programs. Our review has also identified gaps in understanding and suggested priority areas for further research. PMID:24278486

76 FR 67730 - Ocean Transportation Intermediary License Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-02

... Type: New OFF License LF Freight USA LLC dba LF Logistics dba LF Freight dba IDS Logistics USA, dba IDS Freight Services, dba AGI Logistics USA, dba AGI Logistics, 230-59 International Airport Center Blvd., 270... Individual), Caetano R. Lopes, Vice President, Application Type: Add NVO Service Eztrans Logistics Ltd. (NVO...

Low-frequency components in harbor porpoise (Phocoena phocoena) clicks: communication signal, by-products, or artifacts?

PubMed

Hansen, M; Wahlberg, M; Madsen, P T

2008-12-01

Underwater sound signals for biosonar and communication normally have different source properties to serve the purposes of generating efficient acoustic backscatter from small objects or conveying information to conspecifics. Harbor porpoises (Phocoena phocoena) are nonwhistling toothed whales that produce directional, narrowband, high-frequency (HF) echolocation clicks. This study tests the hypothesis that their 130 kHz HF clicks also contain a low-frequency (LF) component more suited for communication. Clicks from three captive porpoises were analyzed to quantify the LF and HF source properties. The LF component is 59 (S.E.M=1.45 dB) dB lower than the HF component recorded on axis, and even at extreme off-axis angles of up to 135 degrees , the HF component is 9 dB higher than the LF component. Consequently, the active space of the HF component will always be larger than that of the LF component. It is concluded that the LF component is a by-product of the sound generator rather than a dedicated pulse produced to serve communication purposes. It is demonstrated that distortion and clipping in analog tape recorders can explain some of the prominent LF components reported in earlier studies, emphasizing the risk of erroneous classification of sound types based on recording artifacts.

Solitons of the coupled Schrödinger-Korteweg-de Vries system with arbitrary strengths of the nonlinearity and dispersion

NASA Astrophysics Data System (ADS)

Gromov, Evgeny; Malomed, Boris

2017-11-01

New two-component soliton solutions of the coupled high-frequency (HF)—low-frequency (LF) system, based on Schrödinger-Korteweg-de Vries (KdV) system with the Zakharov's coupling, are obtained for arbitrary relative strengths of the nonlinearity and dispersion in the LF component. The complex HF field is governed by the linear Schrödinger equation with a potential generated by the real LF component, which, in turn, is governed by the KdV equation including the ponderomotive coupling term, representing the feedback of the HF field onto the LF component. First, we study the evolution of pulse-shaped pulses by means of direct simulations. In the case when the dispersion of the LF component is weak in comparison to its nonlinearity, the input gives rise to several solitons in which the HF component is much broader than its LF counterpart. In the opposite case, the system creates a single soliton with approximately equal widths of both components. Collisions between stable solitons are studied too, with a conclusion that the collisions are inelastic, with a greater soliton getting still stronger, and the smaller one suffering further attenuation. Robust intrinsic modes are excited in the colliding solitons. A new family of approximate analytical two-component soliton solutions with two free parameters is found for an arbitrary relative strength of the nonlinearity and dispersion of the LF component, assuming weak feedback of the HF field onto the LF component. Further, a one-parameter (non-generic) family of exact bright-soliton solutions, with mutually proportional HF and LF components, is produced too. Intrinsic dynamics of the two-component solitons, induced by a shift of their HF component against the LF one, is also studied, by means of numerical simulations, demonstrating excitation of a robust intrinsic mode. In addition to the above-mentioned results for LF-dominated two-component solitons, which always run in one (positive) velocities, we produce HF-dominated soliton complexes, which travel in the opposite (negative) direction. They are obtained in a numerical form and by means of a quasi-adiabatic analytical approximation. The solutions with positive and negative velocities correspond, respectively, to super- and subsonic Davydov-Scott solitons.

Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

PubMed

Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

2009-09-01

Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

Eyeball Pressure Stimulation Unveils Subtle Autonomic Cardiovascular Dysfunction in Persons with a History of Mild Traumatic Brain Injury.

PubMed

Hilz, Max J; Aurnhammer, Felix; Flanagan, Steven R; Intravooth, Tassanai; Wang, Ruihao; Hösl, Katharina M; Pauli, Elisabeth; Koehn, Julia

2015-11-15

After mild traumatic brain injury (mTBI), patients have increased long-term mortality rates, persisting even beyond 13 years. Pathophysiology is unclear. Yet, central autonomic network dysfunction may contribute to cardiovascular dysregulation and increased mortality. Purely parasympathetic cardiovascular challenge by eyeball pressure stimulation (EP), might unveil subtle autonomic dysfunction in post-mTBI patients. We investigated whether mild EP shows autonomic cardiovascular dysregulation in post-mTBI patients. In 24 patients (34 ± 12 years; 5-86 months post-injury) and 27 controls (30 ± 11 years), we monitored respiration, electrocardiographic RR intervals (RRI), systolic and diastolic blood pressure (BPsys, BPdia) before and during 2 min of 30 mm Hg EP, applied by an ophthalmologic ocular pressure device (Okulopressor(®)). We calculated spectral powers of RRI in the mainly sympathetic low frequency (LF; 0.04-0.15 Hz) and parasympathetic high frequency (HF; 0.15-0.5 Hz) ranges, and of BP in the sympathetic LF range, the RRI-LF/HF ratio as index of the sympathetic-parasympathetic balance, normalized (nu) RRI-LF- and HF-powers, and LF- and HF-powers after natural logarithmic transformation (ln). Parameters before and during EP in post-mTBI patients and controls were compared by repeated measurement analysis of variance with post hoc analysis (p < 0.05). During EP, BPsys and BPdia increased in post-mTBI patients. Only in controls but not in post-mTBI patients, EP increased RRI-HFnu-powers and decreased RRI-LF-powers, RRI-LFnu-powers, BPsys-LF-powers, BPsys-lnLF-powers and BPdia-lnLF-powers. RRI-LF/HF ratios slightly increased in post-mTBI patients but slightly decreased in controls upon EP. Even with only mild EP, our controls showed normal EP responses and shifted sympathetic-parasympathetic balance towards parasympathetic predominance. In contrast, our post-mTBI patients could not increase parasympathetic heart rate modulation but increased BP upon EP, indicating a paradox sympathetic activation. The findings support the hypothesis that central autonomic dysfunction might contribute to an increased cardiovascular risk, even years after mTBI.

Ectopic expression of Cripto-1 in transgenic mouse embryos causes hemorrhages, fatal cardiac defects and embryonic lethality

PubMed Central

Lin, Xiaolin; Zhao, Wentao; Jia, Junshuang; Lin, Taoyan; Xiao, Gaofang; Wang, Shengchun; Lin, Xia; Liu, Yu; Chen, Li; Qin, Yujuan; Li, Jing; Zhang, Tingting; Hao, Weichao; Chen, Bangzhu; Xie, Raoying; Cheng, Yushuang; Xu, Kang; Yao, Kaitai; Huang, Wenhua; Xiao, Dong; Sun, Yan

2016-01-01

Targeted disruption of Cripto-1 in mice caused embryonic lethality at E7.5, whereas we unexpectedly found that ectopic Cripto-1 expression in mouse embryos also led to embryonic lethality, which prompted us to characterize the causes and mechanisms underlying embryonic death due to ectopic Cripto-1 expression. RCLG/EIIa-Cre embryos displayed complex phenotypes between embryonic day 14.5 (E14.5) and E17.5, including fatal hemorrhages (E14.5-E15.5), embryo resorption (E14.5-E17.5), pale body surface (E14.5-E16.5) and no abnormal appearance (E14.5-E16.5). Macroscopic and histological examination revealed that ectopic expression of Cripto-1 transgene in RCLG/EIIa-Cre embryos resulted in lethal cardiac defects, as evidenced by cardiac malformations, myocardial thinning, failed assembly of striated myofibrils and lack of heartbeat. In addition, Cripto-1 transgene activation beginning after E8.5 also caused the aforementioned lethal cardiac defects in mouse embryos. Furthermore, ectopic Cripto-1 expression in embryonic hearts reduced the expression of cardiac transcription factors, which is at least partially responsible for the aforementioned lethal cardiac defects. Our results suggest that hemorrhages and cardiac abnormalities are two important lethal factors in Cripto-1 transgenic mice. Taken together, these findings are the first to demonstrate that sustained Cripto-1 transgene expression after E11.5 causes fatal hemorrhages and lethal cardiac defects, leading to embryonic death at E14.5-17.5. PMID:27687577

Responsiveness of emulsions stabilized by lactoferrin nano-particles to simulated intestinal conditions.

PubMed

Meshulam, Dafna; Lesmes, Uri

2014-01-01

There is an upsurge of interest in the use of nano-particles to fabricate emulsions and modulate their functionality, with particular emphasis on modulating emulsion digestive fate. Food grade nano-particles formed through controlled processing and electrostatic biopolymer interactions are yet to be systematically studied for their ability to stabilize emulsions and modulate emulsion digestibility. This study focused on the responsiveness of emulsions stabilized by lactoferrin (LF) nano-particles (NPs) and dietary fibers to key digestive parameters. Compared to native LF, LF-NPs comprised emulsion exhibited elevated creaming rates as evident from accelerated stability tests performed by analytical centrifugation. The electrostatic deposition of alginate or carrageenan onto the LF-NPs significantly improved the stability of the corresponding emulsions. Further, the use of various nano-particles showed to have both beneficial and deleterious effects on emulsion responsiveness to pH (2.0 < pH < 10.0), CaCl2 (0-40 mM) and bile (0-25 mg mL(-1)). Simulated pH-stat lipolysis experiments show that the use of LF or LF-NPs had no marked effect on lipolysis. Intriguingly, the use of LF-NPs and alginate reduced emulsion lipolysis by 14% while the use of LF-NPs and carrageenan increased lipolysis by 10%. Microscopy images as well as droplet characterization in terms of size and charge indicate that the altered emulsion responsiveness may be due to physical differences in emulsion properties (e.g. droplet size) and overall organization during digestion (e.g. aggregation vs. coalescence). Overall, this study's insights could prospectively be used to harness protein nano-particles to tweak emulsion behavior during digestion.

Impact of dietary fiber coatings on behavior of protein-stabilized lipid droplets under simulated gastrointestinal conditions.

PubMed

Tokle, Tanushree; Lesmes, Uri; Decker, Eric Andrew; McClements, David Julian

2012-01-01

Multilayer emulsions containing lipid droplets coated by lactoferrin (LF) - anionic polysaccharide layers have improved resistance to environmental stresses (such as pH, salt, and temperature), but their behavior within the gastrointestinal tract (GIT) is currently unknown. The objective of this research was therefore to monitor changes in the physicochemical properties and digestibility of these systems under simulated GIT conditions. Primary emulsions (5% corn oil, 0.5% LF) were prepared using a high-pressure homogenizer. Secondary emulsions (5% corn oil, 0.5% LF, 0.5% polysaccharide) were prepared by incorporating alginate, low methoxyl pectin (LMP) or high methoxyl pectin (HMP) into primary emulsions. Emulsions were then subjected to simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) conditions in sequence. LF, LF-LMP and LF-HMP emulsions were stable to droplet aggregation in the stomach but aggregated in the small intestine, whereas LF-alginate emulsions aggregated in both the stomach and small intestine. The presence of a dietary fiber coating around the initial lipid droplets had little influence on the total extent of lipid digestion in SIF, but LF-alginate emulsions had a slower initial digestion rate than the other emulsions. These results suggest that the dietary fiber coatings may become detached in the small intestine, or that they were permeable to digestive enzymes. Pepsin was found to have little influence on the physical stability or digestibility of the emulsions. The knowledge obtained from this study is important for the design of delivery systems for encapsulation and release of lipophilic bioactive ingredients.

Effects of Static Stretching Exercise on Lumbar Flexibility and Central Arterial Stiffness.

PubMed

Logan, Jeongok G; Kim, Suk-Sun; Lee, Mijung; Byon, Ha Do; Yeo, SeonAe

Previous studies have demonstrated that arterial stiffness is associated with lumbar flexibility (LF). Stretching exercise targeted to improve LF may have a beneficial effect on reducing arterial stiffness. We examined the effects of a single bout of a structured, static stretching exercise on arterial stiffness, LF, peripheral and central blood pressure (BP), and heart rate (HR) and tested the association between LF and central arterial stiffness. The study had a pretest-posttest design without a control group. Thirty healthy women followed a video demonstration of a 30-minute whole-body stretching exercise. Carotid-femoral pulse wave velocity (cf-PWV), augmentation index, LF, peripheral and central BP, and HR were measured before and after the stretching exercise. One bout of a static stretching exercise significantly reduced cf-PWV (t29 = 2.708, P = .011) and HR (t29 = 7.160, P = .000) and increased LF (t29 = 12.248, P < .000). Augmentation index and peripheral and central BP also decreased but did not reach statistical significance. Despite no association found between cf-PWV and LF, the larger increase in LF the subjects had, the larger decrease in cf-PWV they had after exercise (r = 0.500, P = .005). Study findings highlight the potential benefit of a static stretching exercise on central arterial stiffness, an independent predictor of cardiovascular morbidity. Static stretching exercise conducted in the sitting position may be used as an effective intervention to reduce cardiovascular risk after a cardiac event or for patients whose sympathetic function should not be overly activated or whose gaits are not stable.

Functional relationships of landfill and landraise capacity with design and operation parameters.

PubMed

Aivaliotis, Vassilis; Dokas, Ioannis; Hatzigiannakou, Maria; Panagiotakopoulos, Demetrios

2004-08-01

Solid waste management presses for effective landfill design and operation. While planning and operating a landfill (LF) or a landraise (LR), choices need to be made regarding: (1) LF-LR morphology (base shape, side slopes, final cover thickness, LR/LF height/depth); (2) cell geometry (height, length, slopes); and (3) operation parameters (waste density, working face length, cover thicknesses). These parameters affect LF/LR capacity, operation lifespan and construction/ operation costs. In this paper, relationships are generated between capacity (C, space available for waste) and the above parameters. Incorporating real data into simulation kgamma A1.38, runs, two types of functions are developed: first, C = where A is the LF/LR base area size and kgamma a base shape-dependent coefficient; and second, C = alpha(p,gamma,A) + delta(p,gamma,A)Xp for every parameter p, where Xp is the value of p and alpha(p,gamma,A) and delta(p,gamma,A) are parameter- and base (shape/size)-specific coefficients. Moreover, the relationship between LF depth and LR height that balances excavation volume with cover material, is identified. Another result is that, for a symmetrical combination of LF/LR, with base surface area shape between square and 1:2 orthogonal, and final density between 500 and 800 kg m(-3), waste quantity placed ranges from 1.76A1.38 to 2.55A1.38 tons. The significance of such functions is obvious, as they allow the analyst to investigate alternative LF/LR schemes and make trade-off analyses.

Quantum I/f noise in infrared detectors and scanning tunneling microscopes

NASA Astrophysics Data System (ADS)

Truong, Amanda Marie

Noise is, by definition, any random and persistent disturbance, which interferes with the clarity of a signal. Modern electronic devices are designed to limit noise, and in most cases the classical forms of noise have been eliminated or greatly reduced through careful design. However, there is a fundamental, quite unavoidable type of noise, called quantum l/f noise, which occurs at low frequencies and is a fundamental consequence of the discrete nature of the charge carriers themselves. This quantum l/f noise is present in any physical cross section or process rate, such as carrier mobility, diffusion rates and scattering processes. Although quantum l/f noise has been observed for nearly a century, there has been much debate over its origin and formulation. But as modern electronic devices require greater levels of performance and detection, the l/f noise phenomenon has moved to the forefront, becoming the subject of intense research. Here, for the first time, the quantum l/f fluctuations present in both the dark current of the Quantum Well Intersubband Photodetector and the tunneling current of the Scanning Tunneling Microscope are investigated. Using the quantum l/f theory, the quantum l/f noise occurring in each of these devices is formulated. The theoretical noise results are then compared with the experimental findings of various authors with very good agreement. This important work provides a foundation for understanding quantum l/f noise and its causes in the QWIP and STM devices, and could ultimately lead to improved technology and noise reduction in these devices and others.

Antioxidants in vegan diet and rheumatic disorders.

PubMed

Hänninen; Kaartinen, K; Rauma, A L; Nenonen, M; Törrönen, R; Häkkinen, A S; Adlercreutz, H; Laakso, J

2000-11-30

Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. We have clarified the efficacy of LF in rheumatoid diseases as an example of a health problem where inflammation is one of the main concerns. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E. The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. Also the increases of vitamin C and vitamin E (adjusted to cholesterol) were statistically significant. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls. The LF diet is rich in fibre, substrate of lignan production, and the urinary excretion of polyphenols like enterodiol and enterolactone as well as secoisolaricirecinol were much increased in subjects eating LF. The shift of fibromyalgic subjects to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self-experienced health. The rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms. In conclusion the rheumatoid patients subjectively benefited from the vegan diet rich in antioxidants, lactobacilli and fibre, and this was also seen in objective measures.

Effects of single and combined low frequency electromagnetic fields and simulated microgravity on gene expression of human mesenchymal stem cells during chondrogenesis

PubMed Central

Hammerschmid, Florian; Blum, Helmut; Krebs, Stefan; Redeker, Julia I.; Holzapfel, Boris M.; Jansson, Volkmar; Müller, Peter E.

2016-01-01

Introduction Low frequency electromagnetic fields (LF-EMF) and simulated microgravity (SMG) have been observed to affect chondrogenesis. A controlled bioreactor system was developed to apply LF-EMF and SMG singly or combined during chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in 3D culture. Material and methods An external motor gear SMG bioreactor was combined with magnetic Helmholtz coils for EMF (5 mT; 15 Hz). Pellets of hMSCs (±TGF-β3) were cultured (P5) under SMG, LF-EMF, LF-EMF/SMG and control (1 g) conditions for 3 weeks. Sections were stained with safranin-O and collagen type II. Gene expression was evaluated by microarray and real-time polymerase chain reaction analysis. Results Simulated microgravity application significantly changed gene expression; specifically, COLXA1 but also COL2A1, which represents the chondrogenic potential, were reduced (p < 0.05). Low frequency electromagnetic fields application showed no gene expression changes on a microarray basis. LF-EMF/SMG application obtained significant different expression values from cultures obtained under SMG conditions with a re-increase of COL2A1, therefore rescuing the chondrogenic potential, which had been lowered by SMG. Conclusions Simulated microgravity lowered hypertrophy but also the chondrogenic potential of hMSCs. Combined LF-EMF/SMG provided a rescue effect of the chondrogenic potential of hMSCs although no LF-EMF effect was observed under optimal conditions. The study provides new insights into how LF-EMF and SMG affect chondrogenesis of hMSCs and how they generate interdependent effects. PMID:29765449

The effects of instruction and hand dominance on grip-to-load force coordination in manipulation tasks.

PubMed

Jin, Xin; Uygur, Mehmet; Getchell, Nancy; Hall, Susan J; Jaric, Slobodan

2011-10-31

The force applied upon a vertically oriented hand-held object could be decomposed into two orthogonal and highly coordinated components: the grip force (GF; the component perpendicular to the hand-object contact area that provides friction) and the load force (LF; the parallel component that can move the object or support the body). The aim of this study was to investigate the underexplored effects of task instruction and hand dominance on GF-LF coordination. Sixteen right-handed subjects performed bimanual manipulation against a horizontally oriented instrumented device under different sets of instructions. The tasks involved exertion of ramp-and-hold or oscillation patterns of LF performed symmetrically with two hands, while the instructions regarding individual actions were either similar (pull with both hands) or dissimilar (pull with one hand and hold with another). The results revealed that the instruction "to pull" leads to higher indices of GF-LF coordination than the instruction "to hold", as evidenced by a lower GF-LF ratio, higher GF-LF coupling, and higher GF modulation. The only effect of hand dominance was a moderate time lag of GF relative to LF changes observed in the non-dominant hand. We conclude that the instructions could play an important role in GF-LF coordination and, therefore, they should be taken into account when exploring or routinely testing hand function. Additionally, the results suggest that the neural control of GF of the non-dominant hand could involve some feedback mechanisms. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Experimental study on the human thermal comfort based on the heart rate variability (HRV) analysis under different environments.

PubMed

Zhu, Hui; Wang, Hanqing; Liu, Zhiqiang; Li, Duanru; Kou, Guangxiao; Li, Can

2018-03-01

In order to study the human thermal comfort under different environments, the electrocardiogram (ECG) data of 6 subjects were recorded continuously under 60 environments composed by different air temperature, relative humidity and air speed that were created by an environmental chamber. Based on the ECG data, the frequency-domain method was adopted to obtain the heart rate variability (HRV) results. Among the HRV indices, the ratio of the low frequency power and high frequency power of the HRV analysis results (LF/HF), which reflects the balance of the autonomic nervous system, was selected as an indicator of the thermal comfort in the study. And the effects of air temperature, relative humidity and air speed on LF/HF were scrutinized. Meanwhile, a questionnaire survey was conducted during the experiment to evaluate the thermal comfort of the subjects. And the relationships between mean LF/HF and thermal sensation, mean thermal comfort were established based on the survey. The results showed that different LF/HF was observed under different environments, and that the air temperature had the most significant effects on LF/HF. The changes in the air temperature could easily lead to the excitation of the sympathetic nerve that could promote the activities of the thermoregulatory effectors thus thermal discomfort. Additionally, the fitting curves illustrating the relationships between LF/HF and thermal sensation and thermal comfort showed that the higher LF/HF yielded thermal discomfort, while the low LF/HF indicated a thermally acceptable state. Copyright © 2017 Elsevier B.V. All rights reserved.

"Lactoferrin and Peptide-derivatives: Antimicrobial Agents with Potential Use in Nonspecific Immunity Modulation".

PubMed

Drago-Serrano, Maria Elisa; Campos-Rodriguez, Rafael; Carrero, Julio Cesar; de la Garza, Mireya

2018-03-27

Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action in a wide array of pathogens. In addition, they display regulatory properties on components of nonspecific immunity, including toll-like receptors, pro- and anti-inflammatory cytokines, and reactive oxygen species. Mechanisms explaining the ability of Lf and Lfcins to display both up- and down-modulatory properties on cells are not fully understood but result, in part, from their interactions with membrane receptors that elicit biochemical signal pathways, whereas other receptors enable the nuclear translocation of these molecules for the modulation of target genes. The dual role of Lf and Lfcins as antimicrobials and immunomodulators is of biotechnological and pharmaceutical interest. Native Lf and its peptide-derivatives from human and bovine sources, the recombinant versions of the human protein, and their synthetic peptides have potential application as adjunctive agents in therapies to combat infections caused by multi-resistant bacteria and those caused by fungi, protozoa and viruses, as well as in the prevention and reduction of several types of cancer and response to LPS-shock, among other effects. In this review, we summarize the immunomodulatory properties of the unique multifunctional protein Lf and its N-terminus peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Interfacial engineering using mixed protein systems: emulsion-based delivery systems for encapsulation and stabilization of β-carotene.

PubMed

Mao, Yingyi; Dubot, Marie; Xiao, Hang; McClements, David Julian

2013-05-29

Emulsion-based delivery systems are needed to encapsulate, protect, and deliver lipophilic bioactive components in the food, personal care, and pharmaceutical industries. The functional performance of these systems can be controlled by engineering the composition and structure of the interfacial layer coating the lipid droplets. In this study, interfacial properties were controlled using two globular proteins with widely differing isoelectric points: lactoferrin (LF: pI ≈ 8.5) and β-lactoglobulin (BLG: pI ≈ 5). Oil-in-water emulsions were prepared with different interfacial properties: [LF]-only; [BLG]-only; [LF]-[BLG]-(laminated); [BLG]-[LF]-(laminated); and [BLG/LF]-(mixed). The influence of pH, ionic strength, and temperature on the physical stability of β-carotene-enriched emulsions was investigated. [LF]-emulsions were stable to droplet aggregation from pH 2 to 9 (0 mM NaCl), but all other emulsions aggregated at intermediate pH values. [BLG]-emulsions aggregated at high salt levels (≥50 mM NaCl), but all other emulsions were stable (0 to 300 mM NaCl). [BLG/LF]-emulsions were unstable to heating (≥60 °C), but all other emulsions were stable (30 to 90 °C). Color fading due to β-carotene degradation occurred relatively quickly in [BLG]-emulsions (37 °C) but was considerably lower in all other emulsions, which was attributed to the ability of LF to bind iron or interact with β-carotene. This study provides useful information for designing emulsion-based delivery systems to encapsulate and protect bioactive lipids, such as carotenoids.

Antibacterial activity in bovine lactoferrin-derived peptides.

PubMed Central

Hoek, K S; Milne, J M; Grieve, P A; Dionysius, D A; Smith, R

1997-01-01

Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B) were generated from bovine lactoferrin (Lf) with recombinant chymosin. Two peptides were copurified, one identical to Lf-cin B and another differing from Lf-cin B by the inclusion of a C-terminal alanine (lactoferricin). Two other peptides were copurified from chymosin-hydrolyzed Lf, one differing from Lf-cin B by the inclusion of C-terminal alanyl-leucine and the other being a heterodimer linked by a disulfide bond. These peptides were isolated in a single step from chymosin-hydrolyzed Lf by membrane ion-exchange chromatography and were purified by reverse-phase high-pressure liquid chromatography (HPLC). They were characterized by N-terminal Edman sequencing, mass spectrometry, and antibacterial activity determination. Pure lactoferricin, prepared from pepsin-hydrolyzed Lf, was purified by standard chromatography techniques. This peptide was analyzed against a number of gram-positive and gram-negative bacteria before and after reduction of its disulfide bond or cleavage after its single methionine residue and was found to inhibit the growth of all the test bacteria at a concentration of 8 microM or less. Subfragments of lactoferricin were isolated from reduced and cleaved peptide by reverse-phase HPLC. Subfragment 1 (residues 1 to 10) was active against most of the test microorganisms at concentrations of 10 to 50 microM. Subfragment 2 (residues 11 to 26) was active against only a few microorganisms at concentrations up to 100 microM. These antibacterial studies indicate that the activity of lactoferricin is mainly, but not wholly, due to its N-terminal region. PMID:8980754

Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson's disease treatment.

PubMed

Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.

Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

PubMed Central

Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

2016-01-01

Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. PMID:27994458

Complete genomic sequence of the Lactobacillus temperate phage LF1.

PubMed

Yoon, Bo Hyun; Chang, Hyo Ihl

2011-10-01

Bacteriophage LF1, a newly isolated temperate phage from a mitomycin-C-induced lysate of wild type Lactobacillus fermentum, was found to contain a double-strand DNA of 42,606 base pairs (bp) with a G+C content of 45%. Bioinformatic analysis of the phage genome revealed 57 putative open reading frames (ORFs). The predicted protein products of ORFs were determined and described. According to morphological analysis by transmission electron microscopy (TEM), LF1 has an isometric head and a non-contractile tail, indicating that it belongs to the family Siphoviridae. The temperate phage LF1 has a good genetic mosaic relationship with ΦPYB5 in the packaging module. To our knowledge, this is first report of genomic sequencing and characterization of temperate phage LF1 from wild-type L. fermentum isolated from Kimchi in Korea.

Lactoferrin-binding proteins in Shigella flexneri.

PubMed Central

Tigyi, Z; Kishore, A R; Maeland, J A; Forsgren, A; Naidu, A S

1992-01-01

The ability of Shigella flexneri to interact with lactoferrin (Lf) was examined with a 125I-labeled protein-binding assay. The percent binding of human lactoferrin (HLf) and bovine lactoferrin (BLf) to 45 S. flexneri strains was 19 +/- 3 and 21 +/- 3 (mean +/- standard error of the mean), respectively. 125I-labeled HLf and BLf binding to strain M90T reached an equilibrium within 2 h. Unlabeled HLf and BLf displaced the 125I-HLf-bacteria interaction in a dose-dependent manner. The Lf-bacterium complex was uncoupled by KSCN or urea, but not by NaCl. The interaction was specific, and approximately 4,800 HLf binding sites (affinity constant [Ka], 690 nM) or approximately 5,700 BLf binding sites (Ka, 104 nM) per cell were estimated in strain M90T by a Scatchard plot analysis. The native cell envelope (CE) and outer membrane (OM) did not reveal Lf-binding components in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, after being boiled, the CE and OM preparations showed three distinct horseradish peroxidase-Lf reactive bands of about 39, 22, and 16 kDa. The 39-kDa component was also reactive to a monoclonal antibody specific for porin (PoI) proteins of members of the family Enterobacteriaceae. The Lf-binding protein pattern was similar with BLf or HLf, for Crb+ and Crb- strains. The protein-Lf complex was dissociable by KSCN or urea and was stable after treatment with NaCl. Variation (loss) in the O chain of lipopolysaccharide (LPS) markedly enhanced the Lf-binding capacity in the isogenic rough strain SFL1070-15 compared with its smooth parent strain, SFL1070. These data establish that Lf binds to specific components in the bacterial OM; the heat-modifiable, anti-PoI-reactive, and LPS-associated properties suggested that the Lf-binding proteins are porins in S. flexneri. Images PMID:1319403

Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

PubMed

Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

2014-04-04

α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

The maternally expressed WRKY transcription factor TTG2 controls lethality in interploidy crosses of Arabidopsis.

PubMed

Dilkes, Brian P; Spielman, Melissa; Weizbauer, Renate; Watson, Brian; Burkart-Waco, Diana; Scott, Rod J; Comai, Luca

2008-12-09

The molecular mechanisms underlying lethality of F1 hybrids between diverged parents are one target of speciation research. Crosses between diploid and tetraploid individuals of the same genotype can result in F1 lethality, and this dosage-sensitive incompatibility plays a role in polyploid speciation. We have identified variation in F1 lethality in interploidy crosses of Arabidopsis thaliana and determined the genetic architecture of the maternally expressed variation via QTL mapping. A single large-effect QTL, DR. STRANGELOVE 1 (DSL1), was identified as well as two QTL with epistatic relationships to DSL1. DSL1 affects the rate of postzygotic lethality via expression in the maternal sporophyte. Fine mapping placed DSL1 in an interval encoding the maternal effect transcription factor TTG2. Maternal parents carrying loss-of-function mutations in TTG2 suppressed the F1 lethality caused by paternal excess interploidy crosses. The frequency of cellularization in the endosperm was similarly affected by both natural variation and ttg2 loss-of-function mutants. The simple genetic basis of the natural variation and effects of single-gene mutations suggests that F1 lethality in polyploids could evolve rapidly. Furthermore, the role of the sporophytically active TTG2 gene in interploidy crosses indicates that the developmental programming of the mother regulates the viability of interploidy hybrid offspring.

Postexposure prophylaxis for Lassa fever: Experience from a recent outbreak in Nigeria.

PubMed

Isa, Samson E; Okwute, Attah; Iraoyah, Kelly O; Nathan, Shehu Y; Simji, Gomerep S; Okolo, Mark O; Anejo-Okopi, Joseph; Spicola, Daria; Isa, Daisy E

2016-01-01

Secondary transmission of Lassa fever (LF) occurs in the community and in health-care facilities, and is associated with high fatality in Nigeria. We investigated the role of oral ribavirin postexposure prophylaxis (orPEP) in preventing LF among the primary contacts of confirmed cases from December 2015 to March 2016. Epidemiological and clinical data of LF contacts were prospectively collected. However, information regarding ribavirin adverse effects (AEs) were collected retrospectively through a telephone interview. High-risk contacts were clinically monitored ΁ orPEP. Thirty-five (94.6%) out of the 37 individuals enrolled in the study were contacts of confirmed LF cases, and friends and family members (54%) constituted the largest group. However, only 29 (83%) individuals were classified as high-risk contacts. Twenty-one (60%) of contacts were prescribed ribavirin with 6 (28.6%) of them reporting AEs. Body weakness (33%) was the most frequent AE, but there was no incidence of treatment discontinuation due to AE. Furthermore, there were no reported cases of LF among all respondents (0%), whether they had orPEP or not. Secondary transmission of LF seems uncommon and the benefit of orPEP is uncertain. Although AEs of ribavirin may not be uncommon, they are rarely serious enough to cause treatment interruption. More emphasis should be on supporting persons looking after LF cases adopt measures that minimize the risks of exposure.

Lactoferrin denaturation induced by anionic surfactants: The role of the ferric ion in the protein stabilization.

PubMed

Ferreira, Gabriel Max Dias; Ferreira, Guilherme Max Dias; Agudelo, Álvaro Javier Patiño; Hudson, Eliara Acipreste; Dos Santos Pires, Ana Clarissa; da Silva, Luis Henrique Mendes

2018-05-11

Here, investigation was made of the interaction between Lactoferrin (Lf) and the anionic surfactants sodium dodecyl sulfate (SDS), sodium dodecylbenzene sulfonate (SDBS), and sodium decyl sulfate (DSS), using isothermal titration calorimetry, Nano differential scanning calorimetry (NanoDSC), and fluorescence spectroscopy. The Lf-surfactant interaction was enthalpically favorable (the integral enthalpy change ranged from -5.99 kJ mol -1 , for SDS at pH 3.0, to -0.61 kJ mol -1 , for DSS at pH 12.0) and promoted denaturation of the protein. The Lf denaturation efficiency followed the order DSS < SDS < SDBS. The extent of binding of the surfactants to Lf strongly depended on pH and the surfactant structure, reaching a maximum value of 505 SDBS molecules per gram of Lf at pH 3.0. The different efficiencies of the surfactants in denaturing Lf were attributed to the balance of hydrophobic and electrostatic interactions, which also depended on pH and the surfactant structure, highlighting the SDBS-tryptophan residue specific interaction, where SDBS acted as a quencher of fluorescence. Interestingly, the NanoDSC and fluorescence measurements showed that the ferric ion bound to Lf increased its stability against denaturation induced by the surfactants. The results have important implications for understanding the influence of surfactants on structural changes in metalloproteins. Copyright © 2017. Published by Elsevier B.V.

The Galactic HII Region Luminosity Function at Infrared and Radio Wavelengths

NASA Astrophysics Data System (ADS)

Mascoop, Joshua; Anderson, Loren; Sandor Makai, Zoltan; Armentrout, William Paul

2018-01-01

HII regions are the clearest indicators of ongoing high-mass star formation. The HII region luminosity function (LF) therefore probes present global star formation properties, and its shape has been related to HII region properties and galaxy Hubble types. Most HII region LF studies to date have been conducted in external galaxies; due to observational difficulties, there have been relatively few studies of the Milky Way HII region LF. Using ~600 HII regions from the WISE Catalog of Galactic HII Regions, we examine the Galactic LF in the first quadrant. Our high-resolution view of Galactic star formation regions allows us to separate nearby sources, and our sample is complete for all HII regions ionized by single O9.5 stars.We analyze the Galactic LF at six infrared wavelengths - where the emission is due to dust - and also at 20 cm, where the emission is from ionized gas. All LFs have a similar shape, showing that infrared LFs can be used in place of ionized gas tracers. All LFs can be described by a single power law with an index of approximately -2, in agreement with previous studes. We find no compelling evidence of a break or "knee" in the LF. Moreover, we see no significant variation in the form of the LF as a function of heliocentric distance, HII region size, or Galactocentric radius.

Competitive and double antibody sandwich ELISA for the quantification of lactoferrins by using monoclonal and chicken egg yolk IgY antibodies.

PubMed

Sunwoo, Hoon; Gujral, Naiyana; Suresh, Mavanur

2011-01-01

Two effective competitive and double antibody sandwich ELISA based on monoclonal (MAb) and chicken egg yolk IgY antibodies were developed to determine lactoferrin (LF) content in infant and milk formulas. Leghorn laying hens were immunized with purified bovine and human LFs to produce anti-bovine LF and anti-human LF IgY antibody in the egg yolk. After 5-8 weeks of the immunization, anti-LF IgY was extracted and analyzed by ELISA. Specific IgY antibodies against LFs cross reacted with human and bovine LFs, examined by ELISA and western-blot assay. Such cross-reactivity suggested the presence of common antigenic determinants between human and bovine LFs. An indirect competitive ELISA was preferred to quantify LF in milk and infant formulas, since the range of detection is 3.125-50 μg/mL, which is broader compared to the biotinylated ELISA system (5-50 ng/mL). As per the indirect competitive ELISA system, IgY at a concentration of the 150 μg/mL was incubated with various concentrations of bovine LF ranged from 0.003-100 μg/mL. The immunoassay was used to estimate the total bovine LF content in the milk samples and infant formulas, ranging from 49.28-80.96 μg/mL and 29.92-60.00 μg/mL, respectively.

Influence of human lactoferrin expression on iron homeostasis, flavonoids, and antioxidants in transgenic tobacco.

PubMed

Kumar, Vinay; Gill, Tejpal; Grover, Sunita; Ahuja, Paramvir Singh; Yadav, Sudesh Kumar

2013-02-01

This study was aimed at to check the influence of human lactoferrin (hLF) expression on iron homeostasis, flavonoids, and antioxidants in transgenic tobacco. Transgenic tobacco expressing hLF cDNA under the control of a CaMV 35S promoter was produced. The iron content as well as chlorophyll content of transgenic tobacco was lower compared to mock and untransformed wild plants. Interestingly, hLF transgenic tobacco showed higher level of transcript expression for genes related to iron content regulation like iron transporter and metal transporter. While expression of genes related to iron storage such as ferritin 1 and ferritin 2 was downregulated. The transcript expression of genes encoding antioxidant enzymes such as glutathione reductase, glutathione-S-transferase, ascorbate peroxidase, and catalase was downregulated in hLF transgenic tobacco compared to controls. Further, the transcript expression of two important genes encoding dihydroflavonol reductase (DFR) and phenylalanine ammonia lyase regulatory enzymes of flavonoid biosynthesis pathway was analyzed. The expression of DFR was found to be downregulated, while PAL expression was upregulated in hLF transgenic tobacco compared to mock and untransformed wild plant. Total phenolics, flavonoids, and proanthocyanidins contents were found to be higher in hLF transgenic tobacco than the mock and untransformed wild plant. Results suggest that hLF expression in transgenic tobacco leads to iron deficiency, downregulation of antioxidant enzymes, and increase in total flavonoids.

Removal of Escherichia coli via low frequency electromagnetic field in riverbank filtration system.

NASA Astrophysics Data System (ADS)

Selamat, Rossitah; Abustan, Ismail; Rizal Arshad, Mohd; Mokhtar Kamal, Nurul Hana

2018-04-01

The removal of Escherichia coli (E. coli) via low frequency of electromagnetic field (LF-EMF) with different magnetic field was studied. LF-EMF is known as a high magnetic susceptibility method, which could affect E. coli growth without the usage of chemicals. The aim of this study was to investigate the removal of E. coli by using LF-EMF in water abstraction for the riverbank filtration (RBF) application. The effect of LF-EMF with the intensity of 2 to 10mT and 50Hz on coiled column of 1mm copper wire at 1 to 6 hours was assessed. The removal of E. coli after exposing to LF-EMF on the column model was measured using most probable number (MPN/100mL) and colonies forming unit (CFU/100mL) methods. Water flows into the column were varied up to 6 hours and with flowrate of 100 mL/min. Experimental results demonstrate that 100% of E. coli was removed at 8mT after 6 hours exposure. The magnetic field at 10mT removed 100% of E. coli after 4 hours exposure. The results obtained in this study proved that the LF-EMF was efficient in E. coli removal from RBF system. These finding indicated that the LF-EMF intensities and time of exposure can affect the removal of E. coli.

The Effect of Massage Therapy on Autonomic Activity in Critically Ill Children

PubMed Central

Guan, Ling; Yuskiv, Nataliya; Skippen, Peter; Brant, Rollin; Kissoon, Niranjan

2014-01-01

Objectives. Our main objective was to describe the effect of foot and hand (F&H) massage on the autonomic nervous system (ANS) activity in children hospitalized in a pediatric intensive care unit (PICU); the secondary objectives were to assess the relationship between ANS function and the clinical severity and to explore the effects of repeated massage sessions on the ANS. Methods. Design was a descriptive experimental study. Intervention was single or six session(s) of F&H massage. ANS function was assessed through the frequency-domain analysis of heart rate variability. Main metrics included high and low frequency power (HF and LF), HF + LF, and LF/HF ratio. Results. Eighteen children participated in the study. A strong Spearman's correlation (ρ = −0.77) was observed between HF + LF and clinical severity. During massage, the parasympathetic activity (measured by HF) increased significantly from baseline (P = 0.04) with a mean percentage increase of 75% (95% CI: 20%∼130%). LF increased by 56% (95% CI: 20%∼92%) (P = 0.026). Repeated sessions were associated with a persistent effect on HF and LF which peaked at the second session and remained stable thereafter. Conclusions. HF + LF is positively correlated with clinical severity. F&H massage can improve the ANS activity and the effect persists when repeated sessions are offered. PMID:25587344

Simultaneous Isolation of Lactoferrin and Lactoperoxidase from Bovine Colostrum by SPEC 70 SLS Cation Exchange Resin

PubMed Central

Liang, Yafei; Wang, Xuewan; Wu, Mianbin; Zhu, Wanping

2011-01-01

In this work, simultaneous isolation of lactoferrin (Lf) and lactoperoxidase (Lp) from defatted bovine colostrum by one-step cation exchange chromatography with SPEC 70 SLS ion-exchange resin was investigated. A RP-HPLC method for Lf and Lp determination was developed and optimized as the following conditions: detection wavelength of 220 nm, flow rate of 1 mL/min and acetonitrile concentration from 25% to 75% within 20 min. The adsorption process of Lf on SPEC 70 SLS resin was optimized using Lf standard as substrate. The maximum static binding capacity of SPEC 70 SLS resin was of 22.0 mg/g resin at 15 °C, pH 7.0 and adsorption time 3 h. The Lf adsorption process could be well described by the Langmuir adsorption isotherm model, with a maximum adsorption capacity of 21.73 mg/g resin at 15 °C. In batch fractionation of defatted colostrum, the binding capacities of SPEC 70 SLS resin for adsorbing Lf and Lp simultaneously under the abovementioned conditions were 7.60 and 6.89 mg/g resin, respectively, both of which were superior to those of CM Sepharose F.F. or SP Sepharose F.F. resins under the same conditions. As a result, SPEC 70 SLS resin was considered as a successful candidate for direct and economic purification of Lf and Lp from defatted colostrum. PMID:22016715

Recombinant lactoferrin (Lf) of Vechur cow, the critical breed of Bos indicus and the Lf gene variants.

PubMed

Anisha, Shashidharan; Bhasker, Salini; Mohankumar, Chinnamma

2012-03-01

Vechur cow, categorized as a critically maintained breed by the FAO, is a unique breed of Bos indicus due to its extremely small size, less fodder intake, adaptability, easy domestication and traditional medicinal property of the milk. Lactoferrin (Lf) is an iron-binding glycoprotein that is found predominantly in the milk of mammals. The full coding region of Lf gene of Vechur cow was cloned, sequenced and expressed in a prokaryotic system. Antibacterial activity of the recombinant Lf showed suppression of bacterial growth. To the best of our knowledge this is the first time that the full coding region of Lf gene of B. indicus Vechur breed is sequenced, successfully expressed in a prokaryotic system and characterized. Comparative analysis of Lf gene sequence of five Vechur cows with B. taurus revealed 15 SNPs in the exon region associated with 11 amino acid substitutions. The amino acid arginine was noticed as a pronounced substitution and the tertiary structure analysis of the BLfV protein confirmed the positions of arginine in the β sheet region, random coil and helix region 1. Based on the recent reports on the nutritional therapies of arginine supplementation for wound healing and for cardiovascular diseases, the higher level of arginine in the lactoferrin protein of Vechur cow milk provides enormous scope for further therapeutic studies. Copyright © 2011 Elsevier B.V. All rights reserved.

The need of adequate information to achieve total compliance of mass drug administration in Pekalongan

NASA Astrophysics Data System (ADS)

Ginandjar, Praba; Saraswati, Lintang Dian; Taufik, Opik; Nurjazuli; Widjanarko, Bagoes

2017-02-01

World Health Organization (WHO) initiated The Global Program to Eliminate Lymphatic Filariasis (LF) through mass drug administration (MDA). Pekalongan started MDA in 2011. Yet the LF prevalence in 2015 remained exceed the threshold (1%). This study aimed to describe the inhibiting factors related to the compliance of MDA in community level. This was a rapid survey with cross sectional approach. A two-stages random sampling was used in this study. In the first stage, 25 clusters were randomly selected from 27 villages with proportionate to population size (PPS) methods (C-Survey). In the second stage, 10 subjects were randomly selected from each cluster. Subject consisted of 250 respondents from 25 selected clusters. Variables consisted of MDA coverage, practice of taking medication during MDA, enabling and inhibiting factors to MDA in community level. The results showed most respondents had poor knowledge on filariasis, which influence awareness of the disease. Health-illness perception, did not receive the drugs, lactation, side effect, and size of the drugs were dominant factors of non-compliance to MDA. MDA information and community empowerment were needed to improve MDA coverage. Further study to explore the appropriate model of socialization will support the success of MDA program

Reexamination of Ball-Race Conformity Effects on Ball Bearing Life

NASA Technical Reports Server (NTRS)

Zaretsky, Erwin V.; Poplawski, Joseph V.; Root, Lawrence E.

2007-01-01

The analysis in this report considers the life of the ball set as well as the respective lives of the races to reassess the effect of ball-race conformity on ball bearing life. The related changes in ball bearing life are incorporated in life factors that can be used to modify the bearing predicted life using the Lundberg-Palmgren equations and the ANSI/ABMA and ISO Standards. Two simple algebraic relationships were established to calculate life factors LF(sub c) to determine the effect of inner- and outer-race conformity combinations on bearing L(sub 10) life for deepgroove and angular-contact ball bearings, respectively. Depending on the bearing type and series as well as conformity combinations, the calculated life for deep-groove ball bearings can be over 40 percent less than that calculated by the Lundberg-Palmgren equations. For angular-contact ball bearings, the life can vary between +16 and -39 percent from that calculated by the Lundberg-Palmgren equations. Comparing the two ball bearing types, the life factors LF(sub c) for the deep-groove bearings can be as much as 40 percent lower than that for angular-contact ball bearings.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way.

PubMed

Chang, Chuan-Chia; Chang, Hsin-An; Chen, Tien-Yu; Fang, Wen-Hui; Huang, San-Yuan

2014-09-01

The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition.

PubMed

Hegazy, Rehab; Salama, Abeer; Mansour, Dina; Hassan, Azza

2016-01-01

Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o.) or (300 mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1.

Exercise frequency, health risk factors, and diseases of the elderly.

PubMed

Kemmler, Wolfgang; von Stengel, Simon

2013-11-01

To determine the effect of exercise frequency on various diseases and risk factors of the elderly. Retrospective analysis of a randomized controlled 18-month exercise trial. University ambulatory group setting. Community-dwelling women aged ≥65 years (N=162) in the area of Northern Bavaria. Mixed, intense aerobic, resistance, and balance protocol for 18 months. Subjects were retrospectively subdivided into 2 groups according to their effective attendance over 18 months (>1-<2 vs ≥2-4 sessions/wk). Bone mineral density (BMD), lean body mass, appendicular skeletal muscle mass by dual-energy x-ray absorptiometry, Framingham study-based 10-year coronary heart disease (CHD) risk, and number of falls by calendar method. Significant differences between the low-frequency exercise group (LF-EG) and the high-frequency exercise group (HF-EG) were observed for lumbar spine BMD (HF-EG, 2.4%±2.8% vs LF-EG, 0.3%±2.2%; P<.001) and proximal femur BMD (HF-EG, 2.4%±2.8% vs LF-EG, -0.5%±1.6%; P=.014), lean body mass (1.6%±3.4% vs 0.3%±2.6%, P=.053), and appendicular skeletal muscle mass (0.9%±4.5% vs -1.3%±3.2%, P=.011). No differences between both exercise groups were observed for 10-year CHD risk (-1.94%±4.14% vs -2.00%±3.13%; P=.943) and number of falls (0.95±1.36 vs 1.03±1.21 falls/person). Comparing the LF-EG with the less active control group (n=47), only nonsignificant effects for fall number (P=.065) and 10-year CHD risk (P=.178) were evaluated. Although this result might not be generalizable across all exercise types and cohorts, it indicates that an overall exercise frequency of at least 2 sessions/wk may be crucial for impacting bone and muscle mass of elderly subjects. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Atomic structure of the murine norovirus protruding domain and sCD300lf receptor complex.

PubMed

Kilic, Turgay; Koromyslova, Anna; Malak, Virginie; Hansman, Grant S

2018-03-21

Human noroviruses are the leading cause of acute gastroenteritis in human. Noroviruses also infect animals such as cow, mice, cat, and dog. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was recently identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and murine norovirus capsid-protruding domain complex at 2.05 Å resolution. We found that the sCD300lf binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. The sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on the sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that the sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf interacting residues were partially conserved in CD300ld, but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms. IMPORTANCE Noroviruses exhibit exquisite host-range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host-range restriction it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrates that noroviruses can interact with carbohydrates, recent work has shown that expression of the protein CD300lf is both necessary and sufficient for murine norovirus infection of mice and binding of the virus to permissive cells. Importantly, the expression of this murine protein by human cells renders them fully permissive for murine norovirus infection, indicating that at least in this case host-range restriction is determined by molecular events that control receptor binding and entry. Defining the atomic-resolution interactions between the norovirus capsid protein and its cognate receptor is essential for a molecular understanding of host-range restriction and norovirus tropism. Copyright © 2018 American Society for Microbiology.

Low-gradient aortic stenosis

PubMed Central

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-01-01

Abstract An important proportion of patients with aortic stenosis (AS) have a ‘low-gradient’ AS, i.e. a small aortic valve area (AVA <1.0 cm2) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA—low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. PMID:27190103

Responses of heart rate variability to acute pain after minor spinal surgery: optimal thresholds and correlation with the numeric rating scale.

PubMed

Sesay, Musa; Robin, Georges; Tauzin-Fin, Patrick; Sacko, Oumar; Gimbert, Edouard; Vignes, Jean-Rodolphe; Liguoro, Dominique; Nouette-Gaulain, Karine

2015-04-01

The autonomic nervous system is influenced by many stimuli including pain. Heart rate variability (HRV) is an indirect marker of the autonomic nervous system. Because of paucity of data, this study sought to determine the optimal thresholds of HRV above which the patients are in pain after minor spinal surgery (MSS). Secondly, we evaluated the correlation between HRV and the numeric rating scale (NRS). Following institutional review board approval, patients who underwent MSS were assessed in the postanesthesia care unit after extubation. A laptop containing the HRV software was connected to the ECG monitor. The low-frequency band (LF: 0.04 to 0.5 Hz) denoted both sympathetic and parasympathetic activities, whereas the high-frequency band (HF: 0.15 to 0.4 Hz) represented parasympathetic activity. LF/HF was the sympathovagal balance. Pain was quantified by the NRS ranging from 0 (no pain) to 10 (worst imaginable pain). Simultaneously, HRV parameters were noted. Optimal thresholds were calculated using receiver operating characteristic curves with NRS>3 as cutoff. The correlation between HRV and NRS was assessed using the Spearman rank test. We included 120 patients (64 men and 56 women), mean age 51±14 years. The optimal pain threshold values were 298 ms for LF and 3.12 for LF/HF, with no significant change in HF. NRS was correlated with LF (r=0.29, P<0.005) and LF/HF (r=0.31, P<0.001) but not with HF (r=0.09, NS). This study suggests that, after MSS, values of LF>298 m and LF/HF>3.1 denote acute pain (NRS>3). These HRV parameters are significantly correlated with NRS.

New methodology to assess activity status of occlusal caries in primary teeth using laser fluorescence device.

PubMed

Braga, Mariana Minatel; de Benedetto, Monique Saveriano; Imparato, Jose Carlos Pettorossi; Mendes, Fausto Medeiros

2010-01-01

An in vivo study was conducted to verify the ability of laser fluorescence (LF) to assess the activity status of occlusal caries in primary teeth, using different air-drying times. Occlusal sites (707) were examined using LF (DIAGNOdent) after air-drying for 3 s and 15 s, and the difference between readings (DIF15 s-3 s) was calculated. For concurrent validation of LF, visual criteria-Nyvad (NY) and Lesion Activity Assessment associated with the International Caries Detection and Assessment System (LAA-ICDAS)-were the reference standards for lesion activity. Histological exam using a pH-indicator dye (0.1% methyl red) was performed in 46 exfoliated/extracted teeth for criterion validation. LF readings and DIF15 s-3 s were compared using Kruskall-Wallis and Mann-Whitney tests. Receiver operating characteristic analyses were performed and validity parameters calculated, considering the caries activity assessment. Using NY, active lesions (3 s: 30.0+/-29.3; 15 s: 34.2+/-30.6) presented higher LF readings than inactive lesions (3 s: 17.0+/-16.3; 15 s: 19.2+/-17.3; p<0.05), different from LAA-ICDAS. Active cavitated caries resulted in higher LF readings (3 s: 50.3+/-3.5; 15 s: 54.7+/-30.2) than inactive cavitated caries (3 s: 19.9+/-16.3; 15 s: 22.8+/-16.8). Therefore, LF can distinguish cavitated active and inactive lesions classified by NY, but not by LAA-ICDAS; however, this difference might be related to the visual system rather than to LF. The air-drying time could be an alternative to improve the caries activity assessment; however, longer air-drying time is suggested to be tested subsequently.

Efficiency of the Lung Flute for sputum induction in patients with presumed pulmonary tuberculosis.

PubMed

Sakashita, Kentaro; Fujita, Akira; Takamori, Mikio; Nagai, Takayuki; Matsumoto, Tomoshige; Saito, Takefumi; Nakagawa, Taku; Ogawa, Kenji; Shigeto, Eriko; Nakatsumi, Yasuto; Goto, Hajime; Mitarai, Satoshi

2018-04-01

High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis. To evaluate the efficiency of the acoustic device (Lung Flute; LF) in sputum induction compared with the conventional method, hypertonic saline inhalation (HSI). In this crossover study, patients with presumed pulmonary tuberculosis submitted 3 consecutive sputa: the first sputum without induction and the second and third ones using LF and HSI. We compared the efficiency of the 2 induction methods. Sixty-four participants were eligible. Thirty-five (54.6%) patients had negative smears on the first sputum without induction. Among those patients, 25.7% and 22.9% patients were smear-positive after using LF and HSI, respectively (P = .001). The positive conversion rate was not significantly different between the methods. The first samples without induction yielded 65.7% positive cultures, whereas 71.4% and 77.1% of the samples from LF and HSI were positive, respectively (P = .284). Similar results were observed in the nucleic acid amplification test [no induction (60.0%), LF (72.0%) and HSI (60.0%); P = .341]. In 29 smear-positive patients on the first sputum without induction, we observed no significant increase in smear grade, culture yield and nucleic acid amplification test positivity with either method. LF tended to induce fewer adverse events; desaturation (3.1% vs 11.1%; P = .082) and throat pain (1.5% vs 9.5%; P = .057). LF showed significantly fewer total adverse events (15.8% vs 34.9%; P = .023). Our study showed LF had similar sputum induction efficiency to HSI with relatively fewer complications. © 2017 The Authors. The Clinical Respiratory Journal Published by John Wiley & Sons Ltd.

High- and low-frequency transcutaneous electrical nerve stimulation does not reduce experimental pain in elderly individuals

PubMed Central

Bergeron-Vézina, Kayla; Corriveau, Hélène; Martel, Marylie; Harvey, Marie-Philippe; Léonard, Guillaume

2015-01-01

Abstract Despite its widespread clinical use, the efficacy of transcutaneous electrical nerve stimulation (TENS) remains poorly documented in elderly individuals. In this randomized, double-blind crossover study, we compared the efficacy of high-frequency (HF), low-frequency (LF), and placebo (P) TENS in a group of 15 elderly adults (mean age: 67 ± 5 years). The effect of HF-, LF-, and P-TENS was also evaluated in a group of 15 young individuals (26 ± 5 years; same study design) to validate the effectiveness of the TENS protocols that were used in the elderly group. Each participant came to the laboratory on 3 separate occasions to receive, in random order, HF-, LF-, and P-TENS. Pain intensity and pain perception thresholds were assessed before, during, and after TENS, using an experimental heat pain paradigm. For the young group, there was a significant decrease in pain intensity during and after HF- and LF-TENS when compared with baseline, with both HF- and LF-TENS being superior to P-TENS. In the older group, HF- and LF-TENS did not reduce pain when compared with baseline and no difference was observed between the 2 active TENS sessions and P-TENS. High-frequency, LF-, and P-TENS all increased pain thresholds in young individuals, whereas in older individuals, only LF-TENS increased pain thresholds. Taken together, these results suggest that TENS is effective in young, but not in older, individuals. Future studies should be conducted to confirm these results in pain populations and to identify strategies that could enhance the effect of TENS in the elderly. PMID:26101836

Linear and nonlinear winter atmospheric responses to extreme phases of low frequency Pacific sea surface temperature variability

NASA Astrophysics Data System (ADS)

Cao, Dandan; Wu, Qigang; Hu, Aixue; Yao, Yonghong; Liu, Shizuo; Schroeder, Steven R.; Yang, Fucheng

2018-02-01

This study examines Northern Hemisphere winter (DJFM) atmospheric responses to opposite strong phases of interdecadal (low frequency, LF) Pacific sea surface temperature (SST) forcing, which resembles El Niño-Southern Oscillation (ENSO) on a longer time scale, in observations and GFDL and CAM4 model simulations. Over the Pacific-North America (PNA) sector, linear observed responses of 500-hPa height (Z500) anomalies resemble the PNA teleconnection pattern, but show a PNA-like nonlinear response because of a westward Z500 shift in the negative (LF-) relative to the positive LF (LF+) phase. Significant extratropical linear responses include a North Atlantic Oscillation (NAO)-like Z500 anomaly, a dipole-like Z500 anomaly over northern Eurasia associated with warming over mid-high latitude Eurasia, and a Southern Annular anomaly pattern associated with warming in southern land areas. Significant nonlinear Z500 responses also include a NAO-like anomaly pattern. Models forced by LF+ and LF- SST anomalies reproduce many aspects of observed linear and nonlinear responses over the Pacific-North America sector, and linear responses over southern land, but not in the North Atlantic-European sector and Eurasia. Both models simulate PNA-like linear responses in the North Pacific-North America region similar to observed, but show larger PNA-like LF+ responses, resulting in a PNA nonlinear response. The nonlinear PNA responses result from both nonlinear western tropical Pacific rainfall changes and extratropical transient eddy feedbacks. With LF tropical Pacific forcing only (LFTP+ and LFTP-, climatological SST elsewhere), CAM4 simulates a significant NAO response to LFTP-, including a linear negative and nonlinear positive NAO response.

Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and immune cells in the large intestine.

PubMed

Iigo, Masaaki; Alexander, David B; Xu, Jiegou; Futakuchi, Mitsuru; Suzui, Masumi; Kozu, Takahiro; Akasu, Takayuki; Saito, Daizo; Kakizoe, Tadao; Yamauchi, Koji; Abe, Fumiaki; Takase, Mitsunori; Sekine, Kazunori; Tsuda, Hiroyuki

2014-10-01

Studies using animal models have demonstrated that ingestion of bovine lactoferrin (bLF) inhibits carcinogenesis in the colon and other organs of experimental animals. As a result of these studies, a blinded, randomized, controlled clinical trial was conducted in the National Cancer Center Hospital, Tokyo, Japan to determine whether ingestion of bLF had an effect on the growth of colorectal polyps in humans. Patients with colorectal polyps ≤5 mm diameter and likely to be adenomas ingested 0, 1.5, or 3.0 g bLF daily for 1 year. Ingestion of 3.0 g bLF suppressed the growth of colorectal polyps and increased the level of serum human lactoferrin in trial participants 63 years old or younger. The purpose of the present study was to investigate correlations between immune parameters and changes in polyp size. Trial participants with regressing polyps had increased NK cell activity, increased serum hLF levels (indicating increased neutrophil activity), and increased numbers of CD4+ cells in the polyps. These findings are consistent with a correlation between higher immune activity and suppression of colorectal polyps. In addition, participants with regressing polyps had lower numbers of PMNs and increased numbers of S100A8+ cells in the polyps, consistent with a correlation between lower inflammatory potential in the colon and suppression of colorectal polyps. Trial participants ingesting bLF had increased serum hLF levels, a possible increase in systemic NK cell activity, and increased numbers of CD4+ and CD161+ cells in the polyps. Taken together, our findings suggest that bLF suppressed colorectal polyps by enhancing immune responsiveness.

Leptospermum flavescens Constituent-LF1 Causes Cell Death through the Induction of Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

PubMed Central

Navanesan, Suerialoasan; Abdul Wahab, Norhanom; Manickam, Sugumaran; Sim, Kae Shin

2015-01-01

Leptospermum flavescens Sm. (Myrtaceae), locally known as ‘Senna makki’ is a smallish tree that is widespread and recorded to naturally occur in the montane regions above 900 m a.s.l from Burma to Australia. Although the species is recorded to be used traditionally to treat various ailments, there is limited data on biological and chemical investigations of L. flavescens. The aim of the present study was to investigate and understand the ability of L. flavescens in inducing cell death in lung cancer cells. The cytotoxic potentials of the extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as a semi pure fraction, LF1) were evaluated against two human non-small cell lung carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the greatest cytotoxic effect against both cell lines with IC50 values of 7.12 ± 0.07 and 9.62 ± 0.50 μg/ml respectively. LF1 treated cells showed a sub-G1 region in the cell cycle analysis and also caused the presence of apoptotic morphologies in cells stained with acridine orange and ethidium bromide. Treatment with LF1 manifested an apoptotic population in cells that were evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1 caused a rise in the presence of activated caspase-3 enzymes in treated cells. Blockage of cell cycle progression was also observed in LF1-treated cells. These findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung cancer cells. Further studies are being conducted to isolate and identify the active compound as well to better understand the mechanism involved in inducing cell death. PMID:26287817

Human Lumbar Ligamentum Flavum Anatomy for Epidural Anesthesia: Reviewing a 3D MR-Based Interactive Model and Postmortem Samples.

PubMed

Reina, Miguel A; Lirk, Philipp; Puigdellívol-Sánchez, Anna; Mavar, Marija; Prats-Galino, Alberto

2016-03-01

The ligamentum flavum (LF) forms the anatomic basis for the loss-of-resistance technique essential to the performance of epidural anesthesia. However, the LF presents considerable interindividual variability, including the possibility of midline gaps, which may influence the performance of epidural anesthesia. We devise a method to reconstruct the anatomy of the digitally LF based on magnetic resonance images to clarify the exact limits and edges of LF and its different thickness, depending on the area examined, while avoiding destructive methods, as well as the dissection processes. Anatomic cadaveric cross sections enabled us to visually check the definition of the edges along the entire LF and compare them using 3D image reconstruction methods. Reconstruction was performed in images obtained from 7 patients. Images from 1 patient were used as a basis for the 3D spinal anatomy tool. In parallel, axial cuts, 2 to 3 cm thick, were performed in lumbar spines of 4 frozen cadavers. This technique allowed us to identify the entire ligament and its exact limits, while avoiding alterations resulting from cutting processes or from preparation methods. The LF extended between the laminas of adjacent vertebrae at all vertebral levels of the patients examined, but midline gaps are regularly encountered. These anatomical variants were reproduced in a 3D portable document format. The major anatomical features of the LF were reproduced in the 3D model. Details of its structure and variations of thickness in successive sagittal and axial slides could be visualized. Gaps within LF previously studied in cadavers have been identified in our interactive 3D model, which may help to understand their nature, as well as possible implications for epidural techniques.

Poincaré plot indexes of heart rate variability detect dynamic autonomic modulation during general anesthesia induction.

PubMed

Hsu, Che-Hao; Tsai, Ming-Ya; Huang, Go-Shine; Lin, Tso-Chou; Chen, Kuen-Pao; Ho, Shung-Tai; Shyu, Liang-Yu; Li, Chi-Yuan

2012-03-01

Beat-to-beat heart rate variability (HRV) is caused by the fluctuating balance of sympathetic and parasympathetic tone. The Poincaré plot has been used to evaluate HRV. In this study, we validate that this new method may qualitatively and quantitatively assess the sympathovagal fluctuation in patients during induction of anesthesia with sevoflurane. Twenty-eight young patients were allocated for the study. The patients received a tilt test and on the next day they sustained anesthesia induced with inhaled anesthetics. Electrocardiography signals from the patients were relayed to an analogue-digital converter. The Poincaré plot is quantified by measuring SD1, SD2, and SD1/SD2. Power spectral analyses were performed and LF, HF and HF/LF were calculated. The LF power and the SD2 of the Poincaré plot increased while subjects were tilt-up from the supine position. Additionally, a significant correlation were found between LF and SD2, HF and SD1 (p < 0.05), and LF/HF and SD2/SD1 (p < 0.01). Sevoflurane inhalation for 10 minutes had no effect on heart rate, but diminished LF, total power and SD1, SD2 of the Poincaré plot respectively. However, the LF, SD2 and LF/HF increased; the HF, SD1 and SD1/SD2 ratio decreased after intubation stimulation. Poincaré plot and power spectral analysis of HRV during tilt test and sevoflurane induction significantly correlate. Poincaré plot analysis is easier and more sensitive at evaluating the sympathovagal balance and observing the beat-to-beat HRV. Copyright © 2012. Published by Elsevier B.V.

[BLG gene knockout and hLF gene knock-in at BLG locus in goat by TALENs].

PubMed

Song, Shaozheng; Zhu, Mengmin; Yuan, Yuguo; Rong, Yao; Xu, Sheng; Chen, Si; Mei, Junyan; Cheng, Yong

2016-03-01

To knock out β-lactoglobulin (BLG) gene and insert human lactoferrin (hLF) coding sequence at BLG locus of goat, the transcription activator-like effector nucleases (TALEN) mediated recombination was used to edit the BLG gene of goat fetal fibroblast, then as donor cells for somatic cell nuclear transfer. We designed a pair of specific plasmid TALEN-3-L/R for goat BLG exon III recognition sites, and BLC14-TK vector containing a negative selection gene HSV-TK, was used for the knock in of hLF gene. TALENs plasmids were transfected into the goat fetal fibroblast cells, and the cells were screened three days by 2 μg/mL puromycin. DNA cleavage activities of cells were verified by PCR amplification and DNA production sequencing. Then, targeting vector BLC14-TK and plasmids TALEN-3-L/R were co-transfected into goat fetal fibroblasts, both 700 μg/mL G418 and 2 μg/mL GCV were simultaneously used to screen G418-resistant cells. Detections of integration and recombination were implemented to obtain cells with hLF gene site-specific integration. We chose targeting cells as donor cells for somatic cell nuclear transfer. The mutagenicity of TALEN-3-L/R was between 25% and 30%. A total of 335 reconstructed embryos with 6 BLG-/hLF+ targeting cell lines were transferred into 16 recipient goats. There were 9 pregnancies confirmed by ultrasound on day 30 to 35 (pregnancy rate of 39.1%), and one of 50-day-old fetus with BLG-/hLF+ was achieved. These results provide the basis for hLF gene knock-in at BLG locus of goat and cultivating transgenic goat of low allergens and rich hLF in the milk.

Recombinase polymerase amplification (RPA) combined with lateral flow (LF) strip for detection of Toxoplasma gondii in the environment.

PubMed

Wu, Y D; Xu, M J; Wang, Q Q; Zhou, C X; Wang, M; Zhu, X Q; Zhou, D H

2017-08-30

Toxoplasma gondii infects all warm-blooded vertebrates, resulting in a great threat to human health and significant economic loss to the livestock industry. Ingestion of infectious oocysts of T. gondii from the environment is the major source of transmission. Detection of T. gondii oocysts by existing methods is laborious, time-consuming and expensive. The objective of the present study was to develop a recombinase polymerase amplification (RPA) method combined with a lateral flow (LF) strip for detection of T. gondii oocysts in the soil and water. The DNA of T. gondii oocysts was amplified by a pair of specific primers based on the T. gondii B1 gene over 15min at a constant temperature ranging from 30°C to 45°C using RPA. The amplification product was visualized by the lateral flow (LF) strip within 5min using the specific probe added to the RPA reaction system. The sensitivity of the established assay was 10 times higher than that of nested PCR with a lower detection limit of 0.1 oocyst per reaction, and there was no cross-reactivity with other closely related protozoan species. Fifty environmental samples were further assessed for the detection validity of the LF-RPA assay (B1-LF-RPA) and compared with nested PCR based on the B1 gene sequence. The B1-LF-RPA and nested PCR both showed that 5 out of the 50 environmental samples were positive. The B1-LF-RPA method was also proven to be sufficiently tolerant of existing inhibitors in the environment. In addition, the advantages of simple operation, speediness and cost-effectiveness make B1-LF-RPA a promising molecular detection tool for T. gondii. Copyright © 2017 Elsevier B.V. All rights reserved.

A low-frequency near-field interferometric-TOA 3-D Lightning Mapping Array

NASA Astrophysics Data System (ADS)

Lyu, Fanchao; Cummer, Steven A.; Solanki, Rahulkumar; Weinert, Joel; McTague, Lindsay; Katko, Alex; Barrett, John; Zigoneanu, Lucian; Xie, Yangbo; Wang, Wenqi

2014-11-01

We report on the development of an easily deployable LF near-field interferometric-time of arrival (TOA) 3-D Lightning Mapping Array applied to imaging of entire lightning flashes. An interferometric cross-correlation technique is applied in our system to compute windowed two-sensor time differences with submicrosecond time resolution before TOA is used for source location. Compared to previously reported LF lightning location systems, our system captures many more LF sources. This is due mainly to the improved mapping of continuous lightning processes by using this type of hybrid interferometry/TOA processing method. We show with five station measurements that the array detects and maps different lightning processes, such as stepped and dart leaders, during both in-cloud and cloud-to-ground flashes. Lightning images mapped by our LF system are remarkably similar to those created by VHF mapping systems, which may suggest some special links between LF and VHF emission during lightning processes.

Characteristics of dilatational infrasonic pulses accompanying low-frequency earthquakes at Miyakejima Volcano, Japan

NASA Astrophysics Data System (ADS)

Fujiwara, Yoshiaki; Yamasato, Hitoshi; Shimbori, Toshiki; Sakai, Takayuki

2014-12-01

Since the caldera-forming eruption of Miyakejima Volcano in 2000, low-frequency (LF) earthquakes have occurred frequently beneath the caldera. Some of these LF earthquakes are accompanied by emergent infrasonic pulses that start with dilatational phases and may be accompanied by the eruption of small amounts of ash. The estimated source locations of both the LF earthquakes and the infrasonic signals are within the vent at shallow depth. Moreover, the maximum seismic amplitude roughly correlates with the maximum amplitude of the infrasonic pulses. From these observations, we hypothesized that the infrasonic waves were excited by partial subsidence within the vent associated with the LF earthquakes. To verify our hypothesis, we used the infrasonic data to estimate the volumetric change due to the partial subsidence associated with each LF earthquake. The results showed that partial subsidence in the vent can well explain the generation of infrasonic waves.

VLF/LF Radio Sounding of Ionospheric Perturbations Associated with Earthquakes

PubMed Central

Hayakawa, Masashi

2007-01-01

It is recently recognized that the ionosphere is very sensitive to seismic effects, and the detection of ionospheric perturbations associated with earthquakes, seems to be very promising for short-term earthquake prediction. We have proposed a possible use of VLF/LF (very low frequency (3-30 kHz) /low frequency (30-300 kHz)) radio sounding of the seismo-ionospheric perturbations. A brief history of the use of subionospheric VLF/LF propagation for the short-term earthquake prediction is given, followed by a significant finding of ionospheric perturbation for the Kobe earthquake in 1995. After showing previous VLF/LF results, we present the latest VLF/LF findings; One is the statistical correlation of the ionospheric perturbation with earthquakes and the second is a case study for the Sumatra earthquake in December, 2004, indicating the spatical scale and dynamics of ionospheric perturbation for this earthquake.

Measured Early Lateral Energy Fractions in Concert Halls and Opera Houses

NASA Astrophysics Data System (ADS)

BARRON, M.

2000-04-01

In the 30 years since early lateral reflections were first suggested as important for concert halls, spatial impression and source broadening have become almost universally accepted as essential characteristics of halls with good acoustics. Two objective measures of source broadening have been proposed. Measured values of the best defined of these measures, the early lateral energy fraction (LF), are considered here. Results from two independent measurement surveys are discussed. Comparisons of LF values by hall show a significant link between hall mean LF and hall width. There is however considerable overlap between measured LF values in different halls so the relevance of describing halls by their mean early lateral energy fraction values is questionable. The behaviour of LF values within auditoria is discussed for different concert hall plan forms and within opera houses. A measure of source broadening including sound level is proposed and results considered in the context of auditorium design.

Short-term heart rate variability (HRV) in healthy dogs.

PubMed

Bogucki, Sz; Noszczyk-Nowak, A

2015-01-01

Heart rate variability (HRV) is a well established mortality risk factor in both healthy dogs and those with heart failure. While the standards for short-term HRV analysis have been developed in humans, only reference values for HRV parameters determined from 24-hour ECG have been proposed in dogs. The aim of this study was to develop the reference values for short-term HRV parameters in a group of 50 healthy dogs of various breeds (age 4.86 ± 2.74 years, body weight 12.2 ± 3.88 kg). The ECG was recorded continuously for at least 180 min in a dark and quiet room. All electrocardiograms were inspected automatically and manually to eliminate atrial or ventricular premature complexes. Signals were transformed into a spectrum using the fast Fourier transform. The HRV parameters were measured at fixed times from 60-min ECG segments. The following time-domain parameters (ms) were analyzed: mean NN, SDNN, SDANN, SDNN index, rMSSD and pNN50. Moreover, frequency-domain parameters (Hz) were determined, including very low frequency (VLF), low frequency (LF) and high frequency (HF) components, total power (TP) and the LF/HF ratio. The results (means ± SD) were as follows: mean NN = 677.68 ± 126.89; SDNN = 208.86 ± 77.1; SDANN = 70.75 ± 30.9; SDNN index = 190.75 ± 76.12; rMSSD = 259 ± 120.17, pNN50 = 71.84 ± 13.96; VLF = 984.96 ± 327.7; LF = 1501.24 ± 736.32; HF = 5845.45 ± 2914.20; TP = 11065.31 ± 3866.87; LF/HF = 0.28 ± 0.11.

FK506-binding protein 10 (FKBP10) regulates lung fibroblast migration via collagen VI synthesis.

PubMed

Knüppel, Larissa; Heinzelmann, Katharina; Lindner, Michael; Hatz, Rudolf; Behr, Jürgen; Eickelberg, Oliver; Staab-Weijnitz, Claudia A

2018-04-19

In idiopathic pulmonary fibrosis (IPF), fibroblasts gain a more migratory phenotype and excessively secrete extracellular matrix (ECM), ultimately leading to alveolar scarring and progressive dyspnea. Here, we analyzed the effects of deficiency of FK506-binding protein 10 (FKBP10), a potential IPF drug target, on primary human lung fibroblast (phLF) adhesion and migration. Using siRNA, FKBP10 expression was inhibited in phLF in absence or presence of 2ng/ml transforming growth factor-β1 (TGF-β1) and 0.1mM 2-phosphoascorbate. Effects on cell adhesion and migration were monitored by an immunofluorescence (IF)-based attachment assay, a conventional scratch assay, and single cell tracking by time-lapse microscopy. Effects on expression of key players in adhesion dynamics and migration were analyzed by qPCR and Western Blot. Colocalization was evaluated by IF microscopy and by proximity ligation assays. FKBP10 knockdown significantly attenuated adhesion and migration of phLF. Expression of collagen VI was decreased, while expression of key components of the focal adhesion complex was mostly upregulated. The effects on migration were 2-phosphoascorbate-dependent, suggesting collagen synthesis as the underlying mechanism. FKBP10 colocalized with collagen VI and coating culture dishes with collagen VI, and to a lesser extent with collagen I, abolished the effect of FKBP10 deficiency on migration. These findings show, to our knowledge for the first time, that FKBP10 interacts with collagen VI and that deficiency of FKBP10 reduces phLF migration mainly by downregulation of collagen VI synthesis. The results strengthen FKBP10 as an important intracellular regulator of ECM remodeling and support the concept of FKBP10 as drug target in IPF.

Community level morbidity control of lymphoedema using self care and integrative treatment in two lymphatic filariasis endemic districts of South India: a non randomized interventional study.

PubMed

Narahari, Saravu R; Bose, Kuthaje S; Aggithaya, Madhur G; Swamy, Gaddam Kumara; Ryan, Terence J; Unnikrishnan, Bhaskaran; Washington, Reynold G; Rao, Balu Palicheralu Sreenivasa; Rajagopala, Shrikrishna; Manjula, Kadengodlu; Vandana, Usha; Sreemol, Thaivalath Anandan; Rojith, Mathew; Salimani, Shanappa Y; Shefuvan, Mohammed

2013-09-01

Currently there is no global program to manage lymphoedema as a result of lymphatic filariasis (LF). The primary aim of this study was to determine the efficacy of a previously proposed integrative treatment protocol, using locally available resources to address the morbidity, in a community village setting. Two LF endemic districts of south India, Gulbarga in Karnataka (GK) and Alleppey in Kerala (AK), were selected for the study. All known patients were invited to an LF camp. Patients with grade two late or three lymphoedema were enrolled. All patients were given training in the integrative procedure which involved patient education and the domiciliary protocol. A total of 730 patients (851 limbs) completed the three and half month follow up. There was a statistically significant (1%) reduction up to mid thigh level volume measurement for both small (0.7-1.1 liters) and large (1.8-5.0 liters) limbs, p < 0.000. In AK inflammatory episodes at the three months interval reduced from 37.5% (127 patients) to 28.3% (96 patients) and in GK from 37.6% (147 patients) to 10.2% (40 patients), p < 0.000. All patients had reduced bacterial entry points. There was an overall improvement in quality of life in all domains of LF specific quality of life questionnaire p < 0.000. Self care and integrative treatment is possible in resource poor Indian village settings. Further work is needed to explore factors leading to better compliance by randomizing the interventions such as washing and emollient compression vs Ayurvedic and yoga interventions before integrative treatment is considered for national health programmes in developing countries.

Efficiency of donor cell preparation and recipient oocyte source for production of transgenic cloned dairy goats harboring human lactoferrin.

PubMed

Wan, Yong-Jie; Zhang, Yan-Li; Zhou, Zheng-Rong; Jia, Ruo-Xin; Li, Meng; Song, Hui; Wang, Zi-Yu; Wang, Li-Zhong; Zhang, Guo-Min; You, Ji-Hao; Wang, Feng

2012-08-01

The objective was to investigate the effects of the transgenic donor cell synchronization method, oocyte sources, and other factors, on production of hLF-gene nucleus transfer dairy goats. Three transfected cell lines from ear biopsies from three 3-mo-old Saanen dairy goats (designated Number 1, Number 2, and Number 3, respectively) were selected as karyoplast donors for somatic cell nuclear transfer (SCNT) after detailed identification (including PCR and sequencing of PCR products). In donor cell cycle synchronization studies, the apoptosis rate of hLF transgenic fibroblasts was not different (P > 0.05) after 3 days of serum starvation or 2 days of contact inhibition. Additionally, there was no effect (P > 0.05) on developmental capacity of reconstructed embryos; however, the kidding rate of recipients in the serum starvation group was higher than that in the contact inhibition group (18 vs. 0%, respectively). The production efficiency of the transgenic cloned goats using donor cells from the Number 1 dairy goat cell line was higher than those using the Number 2 and the Number 3 cell lines (kidding rates were 18, 2, and 0%, respectively, P < 0.05). The oocyte source did not significantly affect the pregnancy rate of hLF-transgenic cloned dairy goats, but more fetuses were aborted when using in vitro matured oocytes compared to in vivo matured oocytes. In summary, utilizing transfected 3-mo-old dairy goat fibroblasts as donor cells, seven live offspring were produced, and the hLF gene was successfully integrated. This study provided additional insights into preparation of donor cells and recipient oocytes for producing transgenic cloned goats through SCNT. Copyright © 2012 Elsevier Inc. All rights reserved.

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

PubMed Central

Seip, Richard L; Volek, Jeff S; Windemuth, Andreas; Kocherla, Mohan; Fernandez, Maria Luz; Kraemer, William J; Ruaño, Gualberto

2008-01-01

Background Genetic factors that predict responses to diet may ultimately be used to individualize dietary recommendations. We used physiogenomics to explore associations among polymorphisms in candidate genes and changes in relative body fat (Δ%BF) to low fat and low carbohydrate diets. Methods We assessed Δ%BF using dual energy X-ray absorptiometry (DXA) in 93 healthy adults who consumed a low carbohydrate diet (carbohydrate ~12% total energy) (LC diet) and in 70, a low fat diet (fat ~25% total energy) (LF diet). Fifty-three single nucleotide polymorphisms (SNPs) selected from 28 candidate genes involved in food intake, energy homeostasis, and adipocyte regulation were ranked according to probability of association with the change in %BF using multiple linear regression. Results Dieting reduced %BF by 3.0 ± 2.6% (absolute units) for LC and 1.9 ± 1.6% for LF (p < 0.01). SNPs in nine genes were significantly associated with Δ%BF, with four significant after correction for multiple statistical testing: rs322695 near the retinoic acid receptor beta (RARB) (p < 0.005), rs2838549 in the hepatic phosphofructokinase (PFKL), and rs3100722 in the histamine N-methyl transferase (HNMT) genes (both p < 0.041) due to LF; and the rs5950584 SNP in the angiotensin receptor Type II (AGTR2) gene due to LC (p < 0.021). Conclusion Fat loss under LC and LF diet regimes appears to have distinct mechanisms, with PFKL and HNMT and RARB involved in fat restriction; and AGTR2 involved in carbohydrate restriction. These discoveries could provide clues to important physiologic mechanisms underlying the Δ%BF to low carbohydrate and low fat diets. PMID:18254975

Cardiopulmonary resuscitation duration and survival in out-of-hospital cardiac arrest patients.

PubMed

Adnet, Frederic; Triba, Mohamed N; Borron, Stephen W; Lapostolle, Frederic; Hubert, Hervé; Gueugniaud, Pierre-Yves; Escutnaire, Josephine; Guenin, Aurelien; Hoogvorst, Astrid; Marbeuf-Gueye, Carol; Reuter, Paul-Georges; Javaud, Nicolas; Vicaut, Eric; Chevret, Sylvie

2017-02-01

Relationship between cardiopulmonary arrest and resuscitation (CPR) durations and survival after out-of-hospital cardiac arrest (OHCA) remain unclear. Our primary aim was to determine the association between survival without neurologic sequelae and cardiac arrest intervals in the setting of witnessed OHCA. We analyzed 27,301 non-traumatic, witnessed OHCA patients in France included in the national registry from June 1, 2011 through December 1, 2015. We analyzed cardiac arrest intervals, designated as no-flow (NF; from collapse to start of CPR) and low-flow (LF; from start of CPR to cessation of resuscitation) in relation to 30-day survival without sequelae. We determined the influence of recognized prognostic factors (age, gender, initial rhythm, location of cardiac arrest) on this relation. For the entire cohort, the area delimited by a value of NF greater than 12min (95% confidence interval: 11-13min) and LF greater than 33min (95% confidence interval: 29-45min), yielded a probability of 30-day survival of less than 1%. These sets of values were greatly influenced by initial cardiac arrest rhythm, age, sex and location of cardiac arrest. Extended CPR duration (greater than 40min) in the setting of initial shockable cardiac rhythm is associated with greater than 1% survival with NF less than 18min. The NF interval was highly influential on the LF interval regardless of outcome, whether return of spontaneous circulation (p<0.001) or death (p<0.001). NF duration must be considered in determining CPR duration in OHCA patients. The knowledge of (NF, LF) curves as function of age, initial rhythm, location of cardiac arrest or gender may aid in decision-making vis-à-vis the termination of CPR or employment of advanced techniques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of running stride frequency in heart rate variability analysis during treadmill exercise testing.

PubMed

Bailón, Raquel; Garatachea, Nuria; de la Iglesia, Ignacio; Casajús, Jose Antonio; Laguna, Pablo

2013-07-01

The analysis and interpretation of heart rate variability (HRV) during exercise is challenging not only because of the nonstationary nature of exercise, the time-varying mean heart rate, and the fact that respiratory frequency exceeds 0.4 Hz, but there are also other factors, such as the component centered at the pedaling frequency observed in maximal cycling tests, which may confuse the interpretation of HRV analysis. The objectives of this study are to test the hypothesis that a component centered at the running stride frequency (SF) appears in the HRV of subjects during maximal treadmill exercise testing, and to study its influence in the interpretation of the low-frequency (LF) and high-frequency (HF) components of HRV during exercise. The HRV of 23 subjects during maximal treadmill exercise testing is analyzed. The instantaneous power of different HRV components is computed from the smoothed pseudo-Wigner-Ville distribution of the modulating signal assumed to carry information from the autonomic nervous system, which is estimated based on the time-varying integral pulse frequency modulation model. Besides the LF and HF components, the appearance is revealed of a component centered at the running SF as well as its aliases. The power associated with the SF component and its aliases represents 22±7% (median±median absolute deviation) of the total HRV power in all the subjects. Normalized LF power decreases as the exercise intensity increases, while normalized HF power increases. The power associated with the SF does not change significantly with exercise intensity. Consideration of the running SF component and its aliases is very important in HRV analysis since stride frequency aliases may overlap with LF and HF components.

76 FR 73489 - Airworthiness Directives; Honeywell International Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... Airworthiness Directives; Honeywell International Inc. Turbofan Engines AGENCY: Federal Aviation Administration...-1F, and LF507-IH turbofan engines. This AD requires removing from service certain second stage high... International Inc. ALF502L-2C, ALF502R-3, ALF502R-3A, ALF502R-5, LF507-1F, and LF507-IH turbofan engines, with...

Defense Environmental Restoration Program Annual Report to Congress for Fiscal Year 1986

DTIC Science & Technology

1987-03-16

LF 01 LANDFILL $3 AND HAROFILL RUFS C SITE LF 02 LANDFILL I RI C SITE LF 03 LANDFILL 2 RI C SITE LU 01 BLDG 2017 -BEA ABANDONED UST FS C SITE tU 02 BLDG...Army Amiunition Plant, Texarkana Hill Air force Base, Ogden Ogden Defense Depot, Ogden Toele Army Depot, Tooele VIFIOIA Defense General Supply Center

The effect of different fibre volume fraction on mechanical properties of banana/pineapple leaf (PaLF)/glass hybrid composite

NASA Astrophysics Data System (ADS)

Hanafee, Z. M.; Khalina, A.; Norkhairunnisa, M.; Syams, Z. Edi; Liew, K. E.

2017-09-01

This paper investigates the effect of fibre volume fraction on mechanical properties of banana-pineapple leaf (PaLF)-glass reinforced epoxy resin under tensile loading. Uniaxial tensile tests were carried out on specimens with different fibre contents (30%, 40%, 50% in weight). The composite specimens consists of 13 different combinations. The effect of hybridisation between synthetic and natural fibre onto tensile properties was determined and the optimum fibre volume fraction was obtained at 50% for both banana and PaLF composites. Additional 1 layer of woven glass fibre increased the tensile strength of banana-PaLF composite up to 85%.

Plasma lactoferrin levels in newborn preterm infants with sepsis.

PubMed

Decembrino, Lidia; DeAmici, Mara; De Silvestri, Annalisa; Manzoni, Paolo; Paolillo, Piermichele; Stronati, Mauro

2017-12-01

Lactoferrin (Lf) is one of the major proteins of all exocrine secretions with a role in the antinfective process. Our aim was to evaluate how plasma Fl levels may change in response to infection in newborn preterm infants. A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age >72 h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study. We found that Lf serum concentration was significantly lowest in four neonates (26.7%) with confirmed sepsis than in 11 (73.3%) with clinical sepsis. The AUC was 0.90 (95%CI: 0.63-0.99). The optimal cutoff for Lf was <1.2 μg/ml with a sensibility of 100% and a specificity of 81.8%. Lf serum concentration was positively correlated with WBC or neutrophil (Spearman rho = 0.69 and 0.49, respectively). Serum Lf could prove a promising, sensitive and specific marker in the diagnostic approach to infants with suspected sepsis, thanks to its role in defense mechanisms and physiological functions of the immune system. Low levels of Lf in sepsis may suggest an immature response due to suboptimal leukocites activity in newborn preterm infants.

Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

PubMed Central

Hooper, Pamela J.; Chu, Brian K.; Mikhailov, Alexei; Ottesen, Eric A.; Bradley, Mark

2014-01-01

Background In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed in 56 endemic countries—it is most appropriate to estimate the impact that the MDA has had on reducing the population at risk of LF. Methodology/Principal Findings To assess GPELF progress in reducing the population at-risk for LF, we developed a model based on defining reductions in risk of infection among cohorts of treated populations following each round of MDA. The model estimates that the number of people currently at risk of infection decreased by 46% to 789 million through 2012. Conclusions/Significance Important progress has been made in the global efforts to eliminate LF, but significant scale-up is required over the next 8 years to reach the 2020 elimination goal. PMID:25411843

Can the individual calibration be modified when laser fluorescence method is used for caries detection?

PubMed

Reyes, Alessandra; Ferreira, Gisele E; Santos, Joyce; Mendes, Fausto M; Imparato, Jose C P; Braga, Mariana M

2013-03-01

Individual calibration (IC) for caries detection methods based on fluorescence is time-consuming, especially for paediatric dentists, if the calibration has to be performed tooth-by-tooth. However, it is not clear how this calibration actually interfere in laser fluorescence (LF) readings. This in vivo study was to verify the influence of different modes of IC on laser fluorescence (LF) readings. Ninety six occlusal and 95 buccal surfaces of 1st permanent molars were examined using LF device after IC performed on control (no IC), the examined teeth, a permanent incisor, a 1st primary molar or a 2nd primary molar. All modes of IC were performed in the same child. Wilcoxon test and Bland-Altman analysis were used to compare the readings. Intraclass correlation coefficients (ICC) were calculated. Laser fluorescence readings without prior calibration were higher than readings performed after any mode of IC and resulted in different values of ICC. After other IC modes, the LF readings were statistically similar. The absence of IC influences LF readings and LF reproducibility, but different IC methods can be considered in clinical practice. © 2012 The Authors. International Journal of Paediatric Dentistry © 2012 BSPD, IAPD and Blackwell Publishing Ltd.

Effects of Enteric-coated Lactoferrin Tablets Containing Lactobacillus brevis subsp. coagulans on Fecal Properties, Defecation Frequency and Intestinal Microbiota of Japanese Women with a Tendency for Constipation: a Randomized Placebo-controlled Crossover Study

PubMed Central

SUZUKI, Noriyuki; MURAKOSHI, Michiaki; ONO, Tomoji; MORISHITA, Satoru; KOIDE, Misao; BAE, Min Jung; TOTSUKA, Mamoru; SHIMIZU, Makoto; SUGIYAMA, Keikichi; NISHINO, Hoyoku; IIDA, Norio

2013-01-01

The effects of oral administration of enteric-coated tablets containing lactoferrin (LF; 100 mg/tablet) and heat-killed Lactobacillus brevis subsp. coagulans FREM BP-4693 (LB; 6×109 bacteria/tablet) on fecal properties were examined in 32 Japanese women (20–60 years of age) with a tendency for constipation (defecation frequency at equal to or less than 10 times/2 weeks) by a double-blind placebo-controlled crossover design. A significant increase in defecation days per week was obserbed in the subjects who ingested the tablets containing LF and LB compared with the placebo group. The number of bifidobacteria in feces also significantly increased compared with the placebo group. In an in vitro study, LF and tryptic hydrolysate of LF, but not peptic hydrolysate of LF, upregulated the growth of Bifidobacterium longum ATCC15707 when added to the culture. These results demonstrate the capability of the enteric-coated tablets containing LF and LB in improving intestinal function and suggest that they have a growth promoting function for bifidobacteria. PMID:24936358

Coacervates of lactotransferrin and β- or κ-casein: structure determined using SAXS.

PubMed

de Kruif, C G Kees; Pedersen, JanSkov; Huppertz, Thom; Anema, Skelte G

2013-08-20

Lactotransferrin (LF) is a large globular protein in milk with immune-regulatory and bactericidal properties. At pH 6.5, LF (M = 78 kDa) carries a net (calculated) charge of +21. β-Casein (BCN) and κ-casein (KCN) are part of the casein micelle complex in milk. Both BCN and KCN are amphiphillic proteins with a molar mass of 24 and 19 kDa and carry net charges of -14 and -4, respectively. Both BCN and KCN form soap-like micelles, with 40 and 65 monomers, respectively. The net negative charges are located in the corona of the micelles. On mixing LF with the caseins, coacervates are formed. We analyzed the structure of these coarcervates using SAXS. It was found that LF binds to the corona of the micellar structures, at the charge neutrality point. BCN/LF and KCN/LF ratios at the charge neutrality point were found to be ~1.2 and ~5, respectively. We think that the findings are relevant for the protection mechanism of globular proteins in bodily fluids where unstructured proteins are abundant (saliva). The complexes will prevent docking of enzymes on specific charged groups on the globular protein.

Process development and economic evaluation of recombinant human lactoferrin expressed in rice grain.

PubMed

Nandi, Somen; Yalda, Dorice; Lu, Stephen; Nikolov, Zivko; Misaki, Ryo; Fujiyama, Kazuhito; Huang, Ning

2005-06-01

In this paper, we show that recombinant human lactoferrin (rhLF) has been stably expressed at 0.5% brown rice flour weight for nine generations. Process development indicates that rhLF can be efficiently extracted from rice flour in 20 mM phosphate buffer (pH 7.0) containing up to 0.5 M NaCl and at a ratio of 1 kg flour to 10 L buffer. After solid/liquid separation, the extract can then be loaded directly onto an ion-exchange column and rhLF can be eluted using 0.8 M NaCl. The resulting rhLF is about 95% pure. A range of biochemical and biophysical analyses were carried out and results indicated that the purified rhLF was identical to its native human counterpart other than its glycosylation. Economic analysis shows that at 600 kg/year scale, the cash cost to produce 1 g of rhLF of pharmaceutical grade is US$ 5.90. Analysis also indicates that the expression level has profound impact on costs related to planting, milling, extraction and purification, thus high level expression of recombinant protein in plants is one of the key parameters for the success of plant made pharmaceuticals.

Effect of a brown seaweed (Laminaria digitata) extract containing laminarin and fucoidan on the quality and shelf-life of fresh and cooked minced pork patties.

PubMed

Moroney, N C; O'Grady, M N; O'Doherty, J V; Kerry, J P

2013-07-01

A spray-dried seaweed extract containing laminarin (L, 9.3%) and fucoidan (F, 7.8%) (L/F extract) from brown seaweed (Laminaria digitata) was added directly to minced pork (M. longissimus dorsi) (LD) at levels of 0.01%, 0.1% and 0.5% (w/w). Fresh and cooked minced pork patties were stored in modified atmosphere packs containing 80% O2:20% CO2 and 70% N2:30% CO2, respectively, for up to 14 days at 4 °C. The L/F extract reduced the surface redness ('a*' values) of fresh patties as a function of concentration. The L/F extract (0.5%) exerted the greatest lipid pro-oxidant activity in fresh patties. The L/F extract (0.5%) significantly decreased (P<0.05) lipid oxidation in cooked patties. The L/F extract had no effect on the microbiological status, pH, water holding capacity (WHC) or cook loss of patties. Pork patties containing 0.01% L/F were preferred by sensory panellists. Further research will focus on the use of refined purified seaweed extracts in functional meat products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Examining the impact of psychiatric diagnosis and comorbidity on the medical lethality of adolescent suicide attempts.

PubMed

McManama O'Brien, Kimberly H; Berzin, Stephanie C

2012-08-01

Specific psychiatric diagnoses and comorbidity patterns were examined to determine if they were related to the medical lethality of suicide attempts among adolescents presenting to an urban general hospital (N=375). Bivariate analysis showed that attempters with substance abuse disorders had higher levels of lethality than attempters without substance abuse. Regression results indicated having depression comorbid with any other diagnosis was not associated with medical lethality. However, having a substance abuse disorder was associated with higher suicide attempt lethality, highlighting the importance of substance abuse as a risk factor for lethal suicide attempts in adolescents. This finding stimulates critical thinking around the understanding of suicidal behavior in youth and the development and implementation of treatment strategies for suicidal adolescents with substance abuse disorders. © 2012 The American Association of Suicidology.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer's disease.

PubMed

Meng, Qingqing; Wang, Aiping; Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang

2018-01-01

Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer's disease (AD). To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. HupA Lf-TMC NPs were prepared using the emulsion-solvent evaporation method and optimized using the Box-Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography-tandem mass spectrometry. Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively. Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier.

The past matters: estimating intrinsic hookworm transmission intensity in areas with past mass drug administration to control lymphatic filariasis.

PubMed

Werkman, Marleen; Truscott, James E; Toor, Jaspreet; Wright, James E; Anderson, Roy M

2017-05-23

Current WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme. Analyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R 0 ). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R 0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R 0 value is predicted to be 1.67. The intrinsic R 0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities. To design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R 0 ). The baseline prevalence alone is not sufficient to inform policy for the control of STH, post cessation of LF MDA, since this will be highly dependent on the intensity and effectiveness of past programmes and the intrinsic transmission intensity of the dominant STH species in any given setting.

Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export.

PubMed

White, Phillip J; Lapworth, Amanda L; An, Jie; Wang, Liping; McGarrah, Robert W; Stevens, Robert D; Ilkayeva, Olga; George, Tabitha; Muehlbauer, Michael J; Bain, James R; Trimmer, Jeff K; Brosnan, M Julia; Rolph, Timothy P; Newgard, Christopher B

2016-07-01

A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES). We performed comprehensive metabolic and physiologic profiling to characterize the effects of BCAA restriction on energy balance, insulin sensitivity, and glucose, lipid and amino acid metabolism. LF-fed ZFR had higher levels of circulating BCAA and lower levels of glycine compared to LF-fed ZLR. Feeding ZFR with the LF-RES diet lowered circulating BCAA to levels found in LF-fed ZLR. Activity of the rate limiting enzyme in the BCAA catabolic pathway, branched chain keto acid dehydrogenase (BCKDH), was lower in liver but higher in skeletal muscle of ZFR compared to ZLR and was not responsive to diet in either tissue. BCAA restriction had very little impact on metabolites studied in liver of ZFR where BCAA content was low, and BCKDH activity was suppressed. However, in skeletal muscle of LF-fed ZFR compared to LF-fed ZLR, where BCAA content and BCKDH activity were increased, accumulation of fatty acyl CoAs was completely normalized by dietary BCAA restriction. BCAA restriction also normalized skeletal muscle glycine content and increased urinary acetyl glycine excretion in ZFR. These effects were accompanied by lower RER and improved skeletal muscle insulin sensitivity in LF-RES fed ZFR as measured by hyperinsulinemic-isoglycemic clamp. Our data are consistent with a model wherein elevated circulating BCAA contribute to development of obesity-related insulin resistance by interfering with lipid oxidation in skeletal muscle. BCAA-dependent lowering of the skeletal muscle glycine pool appears to contribute to this effect by slowing acyl-glycine export to the urine.

Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids.

PubMed

Luscombe-Marsh, Natalie D; Noakes, Manny; Wittert, Gary A; Keogh, Jennifer B; Foster, Paul; Clifton, Peter M

2005-04-01

When substituted for carbohydrate in an energy-reduced diet, dietary protein enhances fat loss in women. It is unknown whether the effect is due to increased protein or reduced carbohydrate. We compared the effects of 2 isocaloric diets that differed in protein and fat content on weight loss, lipids, appetite regulation, and energy expenditure after test meals. This was a parallel, randomized study in which subjects received either a low-fat, high-protein (LF-HP) diet (29 +/- 1% fat, 34 +/- 0.8% protein) or a high-fat, standard-protein (HF-SP) diet (45 +/- 0.6% fat, 18 +/- 0.3% protein) during 12 wk of energy restriction (6 +/- 0.1 MJ/d) and 4 wk of energy balance (7.4 +/- 0.3 MJ/d). Fifty-seven overweight and obese [mean body mass index (in kg/m(2)): 33.8 +/- 0.9] volunteers with insulin concentrations >12 mU/L completed the study. Weight loss (LF-HP group, 9.7 +/- 1.1 kg; HF-SP group, 10.2 +/- 1.4 kg; P = 0.78) and fat loss were not significantly different between diet groups even though the subjects desired less to eat after the LF-HP meal (P = 0.02). The decrease in resting energy expenditure was not significantly different between diet groups (LF-HP, -342 +/- 185 kJ/d; HF-SP, -349 +/- 220 kJ/d). The decrease in the thermic effect of feeding with weight loss was smaller in the LF-HP group than in the HF-SP group (-0.3 +/- 1.0% compared with -3.6 +/- 0.7%; P = 0.014). Glucose and insulin responses to test meals improved after weight loss (P < 0.001) with no significant diet effect. Bone turnover, inflammation, and calcium excretion did not change significantly. The magnitude of weight loss and the improvements in insulin resistance and cardiovascular disease risk factors did not differ significantly between the 2 diets, and neither diet had any detrimental effects on bone turnover or renal function.

Increased Sympathetic and Decreased Parasympathetic Cardiac Tone in Patients with Sleep Related Alveolar Hypoventilation

PubMed Central

Palma, Jose-Alberto; Urrestarazu, Elena; Lopez-Azcarate, Jon; Alegre, Manuel; Fernandez, Secundino; Artieda, Julio; Iriarte, Jorge

2013-01-01

Objective: To assess autonomic function by heart rate variability (HRV) during sleep in patients with sleep related alveolar hypoventilation (SRAH) and to compare it with that of patients with obstructive sleep apnea (OSA) and control patients. Design: Cross-sectional study. Setting: Sleep Unit, University Hospital of University of Navarra. Patients: Fifteen idiopathic and obesity related-SRAH patients were studied. For each patient with SRAH, a patient with OSA, matched in age, sex, body mass index (BMI), minimal oxygen saturation (SatO2), and mean SatO2 was selected. Control patients were also matched in age, sex, and BMI with patients with OSA and those with SRAH, and in apnea/hypopnea index (AHI) with patients with SRAH. Interventions: N/A. Measurements and Results: Time- and frequency-domain HRV measures (R-R, standard deviation of normal-to-normal RR interval [SDNN], very low frequency [VLF], low frequency [LF], high frequency [HF], LF/HF ratio) were calculated across all sleep stages as well as during wakefulness just before and after sleep during a 1-night polysomnography. In patients with SRAH and OSA, LF was increased during rapid eye movement (REM) when compared with control patients, whereas HF was decreased during REM and N1-N2 sleep stages. The LF/HF ratio was equally increased in patients with SRAH and OSA during REM and N1-N2. Correlation analysis showed that LF and HF values during REM sleep were correlated with minimal SatO2 and mean SatO2. Conclusions: Patients with SRAH exhibited an abnormal cardiac tone during sleep. This fact appears to be related to the severity of nocturnal oxygen desaturation. Moreover, there were no differences between OSA and SRAH, supporting the hypothesis that autonomic changes in OSA are primarily related to a reduced nocturnal oxygen saturation, rather than a consequence of other factors such as nocturnal respiratory events. Citation: Palma JA; Urrestarazu E; Lopez-Azcarate J; Alegre M; Fernandez S; Artieda J; Iriarte J. Increased sympathetic and decreased parasym-pathetic cardiac tone in patients with sleep related alveolar hypoventilation. SLEEP 2013;36(6):933-940. PMID:23729937

Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet.

PubMed

Prior, Ronald L; E Wilkes, Samuel; R Rogers, Theodore; Khanal, Ramesh C; Wu, Xianli; Howard, Luke R

2010-04-14

Male C57BL/6J mice (25 days of age) were fed either a low-fat diet (10% kcal from fat) (LF) or a high-fat diet (45% kcal from fat) (HF45) for a period of 72 days. Blueberry juice or purified blueberry anthocyanins (0.2 or 1.0 mg/mL) in the drinking water were included in LF or HF45 treatments. Sucrose was added to the drinking water of one treatment to test if the sugars in blueberry juice would affect development of obesity. Total body weights (g) and body fat (%) were higher and body lean tissue (%) was lower in the HF45 fed mice compared to the LF fed mice after 72 days, but in mice fed HF45 diet plus blueberry juice or blueberry anthocyanins (0.2 mg/mL), body fat (%) was not different from those mice fed the LF diet. Anthocyanins (ACNs) decreased retroperitoneal and epididymal adipose tissue weights. Fasting serum glucose concentrations were higher in mice fed the HF45 diet. However, it was reduced to LF levels in mice fed the HF45 diet plus 0.2 mg of ACNs/mL in the drinking water, but not with blueberry juice. beta cell function (HOMA-BCF) score was lowered with HF45 feeding but returned to normal levels in mice fed the HF45 diet plus purified ACNs (0.2 mg/mL). Serum leptin was elevated in mice fed HF45 diet, and feeding either blueberry juice or purified ACNs (0.2 mg/mL) decreased serum leptin levels relative to HF45 control. Sucrose in drinking water, when consumption was restricted to the volume of juice consumed, produced lower serum leptin and insulin levels, leptin/fat, and retroperitoneal and total fat (% BW). Blueberry juice was not as effective as the low dose of anthocyanins in the drinking water in preventing obesity. Additional studies are needed to determine factors responsible for the differing responses of blueberry juice and whole blueberry in preventing the development of obesity.

Towards elimination of lymphatic filariasis: social mobilization issues and challenges in mass drug administration with anti-filarial drugs in Tamil Nadu, South India.

PubMed

Nandha, B; Krishnamoorthy, K; Jambulingam, P

2013-08-01

India is a signatory to World Health Assembly resolution for elimination of lymphatic filariasis (LF) and National Health Policy has set the goal of LF elimination by 2015. Annual mass drug administration (MDA) is ongoing in endemic districts since 1996-97. Compliance rate is a crucial factor in achieving elimination and was assessed in three districts of Tamil Nadu for 10th and 11th treatment rounds (TRs). An in-depth study assessed the impact of social mobilization by drug distributors (DDs) in two areas from each of the three districts. Overall coverage and compliance for assessed TRs were 76.3 and 67.7% which is below the optimum level to achieve LF elimination. Modifiable determinants continue to be the reason for non-consumption even in the 11th TR and 20.8% were systematic non-compliers. In 76.4% of the cases, DDs failed to adhere to three mandatory visits as per the guidelines. Number of visits by DDs in relation to low and high MDA coverage areas showed a significant relationship (P ≤ 0.000). MDA is limited to drug distribution alone and efforts by DDs in preparing the community were inadequate. Probable means to meet the challenges in preparation of the community is discussed.

Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents.

PubMed

Sondike, Stephen B; Copperman, Nancy; Jacobson, Marc S

2003-03-01

To compare the effects of a low-carbohydrate (LC) diet with those of a low-fat (LF) diet on weight loss and serum lipids in overweight adolescents. A randomized, controlled 12-week trial. Atherosclerosis prevention referral center. Random, nonblinded assignment of participants referred for weight management. The study group (LC) (n = 16) was instructed to consume <20 g of carbohydrate per day for 2 weeks, then <40 g/day for 10 weeks, and to eat LC foods according to hunger. The control group (LF) (n = 14) was instructed to consume <30% of energy from fat. Diet composition and weight were monitored and recorded every 2 weeks. Serum lipid profiles were obtained at the start of the study and after 12 weeks. The LC group lost more weight (mean, 9.9 +/- 9.3 kg vs 4.1 +/- 4.9 kg, P <.05) and had improvement in non-HDL cholesterol levels (P <.05). There was improvement in LDL cholesterol levels (P <.05) in the LF group but not in the LC group. There were no adverse effects on the lipid profiles of participants in either group. The LC diet appears to be an effective method for short-term weight loss in overweight adolescents and does not harm the lipid profile.

Criticisms biologically unwarranted and analytically irrelevant: Reply to Rominger et al.

USGS Publications Warehouse

Bender, L.C.; Weisenberger, M.E.

2009-01-01

The criticisms of Rominger et al. (2008) of our retrospective analysis of desert bighorn sheep (DBS; Ovis canadensis mexicana) dynamics in the San Andres Mountains of south-central New Mexico, USA, contained many biological errors and analytical oversights. Herein, we show that Rominger et al. (2008) 1) overstated both magnitude and potential effect of predator removal; 2) incorrectly claimed that our total precipitation (TP) model did not fit the data when TP correctly classed ???66 of subsequent population increases and declines (P ??? 0.063); 3) presented a necessary prerequisite of the exponential model (serial correlation between Nt and Nt1) as the key relationship in the DBS data, when it merely reflected that DBS are strongly K-selected and was irrelevant to our hypothesis tests specific to factors affecting the instantaneous rate of population increase (r); 4) greatly oversimplified relationships among precipitation, arid environments, and DBS; and 5) advocated a time for collection of lamb/female (L/F) ratio data that was unrelated to any meaningful period in the biological year of DBS and consequently presented L/F ratio data unrelated to observed dynamics of DBS. In contrast, the L/F ratios used in Bender and Weisenberger (2005) correctly predicted annual changes and were correlated with long-term population rates of change.

Does ethnicity matter in risk and protective factors for suicide attempts and suicide lethality?

PubMed Central

Choo, Carol C.; Harris, Keith M.; Chew, Peter K. H.; Ho, Roger C.

2017-01-01

This study explored ethnic differences in risk and protective factors for suicide attempts, for the major ethnic groups in Singapore, and ethnic differences in prediction of lethality. Three years of medical records related to suicide attempters (N = 666) who were admitted to the emergency department of a large teaching hospital in Singapore were subjected to analysis. Of the sample, 69.2% were female, 30.8% male; 63.8% Chinese, 15.8% Indian, and 15.0% Malay. Indians were over-represented in this sample, as compared with the ethnic distribution in the general population. Ages ranged from 10 to 85 years old (M = 29.7, SD = 16.1). Ethnic differences were found in risk and protective factors, and perceived lethality of suicide attempts. All available variables were subjected to regression analyses for Chinese, Indian and Malay attempters to arrive at parsimonious models for prediction of perceived lethality. The findings were discussed in regards to implications in assessment of suicide risk and primary prevention for the multiethnic society in Singapore. PMID:28426687

Development of a time-trend model for analyzing and predicting case-pattern of Lassa fever epidemics in Liberia, 2013-2017.

PubMed

Olugasa, Babasola O; Odigie, Eugene A; Lawani, Mike; Ojo, Johnson F

2015-01-01

The objective was to develop a case-pattern model for Lassa fever (LF) among humans and derive predictors of time-trend point distribution of LF cases in Liberia in view of the prevailing under-reporting and public health challenge posed by the disease in the country. A retrospective 5 years data of LF distribution countrywide among humans were used to train a time-trend model of the disease in Liberia. A time-trend quadratic model was selected due to its goodness-of-fit (R2 = 0.89, and P < 0.05) and best performance compared to linear and exponential models. Parameter predictors were run on least square method to predict LF cases for a prospective 5 years period, covering 2013-2017. The two-stage predictive model of LF case-pattern between 2013 and 2017 was characterized by a prospective decline within the South-coast County of Grand Bassa over the forecast period and an upward case-trend within the Northern County of Nimba. Case specific exponential increase was predicted for the first 2 years (2013-2014) with a geometric increase over the next 3 years (2015-2017) in Nimba County. This paper describes a translational application of the space-time distribution pattern of LF epidemics, 2008-2012 reported in Liberia, on which a predictive model was developed. We proposed a computationally feasible two-stage space-time permutation approach to estimate the time-trend parameters and conduct predictive inference on LF in Liberia.

Maturation of heart rate and blood pressure variability during sleep in term-born infants.

PubMed

Yiallourou, Stephanie R; Sands, Scott A; Walker, Adrian M; Horne, Rosemary S C

2012-02-01

Abnormal blood pressure control is implicated in the sudden infant death syndrome (SIDS). However, no data exist on normal development of blood pressure control during infancy. This study assessed maturation of autonomic control of blood pressure and heart rate during sleep within the first 6 months of life. Term infants (n = 31) were studied longitudinally at 2-4 weeks, 2-3 months, and 5-6 months postnatal age. Infants underwent daytime polysomnography at each age studied. Blood pressure and heart rate were recorded during quiet (QS) and active (AS) sleep in undisturbed baseline and head-up tilt conditions. Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity) and high frequency (HF, parasympathetic activity), total power (LF+HF), and LF/HF ratio (sympathovagal balance). With increasing postnatal age and predominantly during QS, HRV-LF, HRV-HF, and HRV total power increased, while HRV-LF/HF decreased. BPV-LF/HF also decreased with postnatal age. All changes were evident in both baseline and head-up tilt conditions. BPV-LF and BPV total power during tilts were markedly reduced in QS versus AS at each age. In sleeping infants, sympathetic vascular modulation of the circulation decreases with age, while parasympathetic control of heart rate is strengthened. These normative data will aid in the early identification of conditions where autonomic function is impaired, such as in SIDS.

Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells.

PubMed

Hirotani, Yoshihiko; Ikeda, Kenji; Kato, Ryuji; Myotoku, Michiaki; Umeda, Takashi; Ijiri, Yoshio; Tanaka, Kazuhiko

2008-09-01

Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells.

Surface area and volume determination of subgingival calculus using laser fluorescence.

PubMed

Shakibaie, Fardad; Walsh, Laurence J

2014-03-01

Visible red (655 nm) laser fluorescence (LF) devices are currently used for identifying deposits of subgingival calculus on the root surfaces of teeth during dental examination and treatment; however, it is not known how the fluorescence readings produced by commercially available LF systems correlate to the nature of the deposits. This laboratory study explored the correlation between LF digital readings and the surface area and volume of subgingival calculus deposits on teeth. A collection of 30 extracted human posterior teeth with various levels of subgingival deposits of calculus across 240 sites were used in a clinical simulation, with silicone impression material used to replicate periodontal soft tissues. The teeth were scored by two examiners by using three commercial LF systems (DIAGNOdent, DIAGNOdent Pen and KEY3). The silicone was removed, and the teeth were removed for photography at × 20 magnification under white or ultraviolet light. The surface area, thickness, and volume were calculated, and both linear least squares regression and nonlinear (Spearman's rank method) correlation coefficients were determined. Visible red LF digital readings showed better correlation to calculus volume than to surface area. Overall, the best performance was found for the KEY3 system (Spearman coefficient 0.59), compared to the Classic DIAGNOdent (0.56) and the DIAGNOdent Pen (0.49). These results indicate that while visible red LF systems vary somewhat in performance, their LF readings provide a useful estimation of the volume of subgingival calculus deposits present on teeth.

Identification of milk proteins enhancing the antimicrobial activity of lactoferrin and lactoferricin.

PubMed

Murata, M; Wakabayashi, H; Yamauchi, K; Abe, F

2013-08-01

Lactoferrin (LF) is known as an iron-binding antimicrobial protein present in exocrine secretions such as milk and releases the potent antimicrobial peptide lactoferricin (LFcin) by hydrolysis with pepsin. The antimicrobial activity of LF and LFcin has been studied well; however, their cooperative action with other milk proteins remains to be elucidated. In this study, we identified milk proteins enhancing the antimicrobial activity of bovine LF and LFcin against gram-negative bacteria, gram-positive bacteria, and fungi. As the target fraction, we isolated a minor milk protein fraction around 15 kDa, which was identified as bovine RNase 5 (angiogenin-1), RNase 4, and angiogenin-2 by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. As these proteins are collectively known as the RNase A family, we referred to the target protein fraction as milk RNase of 15 kDa (MR15). The number of colony-forming units of Escherichia coli and other pathogenic microorganisms with the addition of MR15 to LF (MR15:LF ratio=16:1,000) was dramatically lowered than that with LF alone. On the other hand, MR15 itself did not show any reductions in the number of colony-forming units at the concentrations tested. Similarly, the antimicrobial activities of LFcin against various microorganisms were significantly enhanced by the addition of MR15. These results suggest that LF and MR15 may be concomitantly acting antimicrobial agents in milk. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

What Do The Trainees Want? (A Symposium on Training 4)

ERIC Educational Resources Information Center

Stock, Arthur

1971-01-01

Author summarizes the results of his survey of teachers of adults which attempted to show the relationship between the training involvement of teachers and various other factors. Attitudes to courses, opinions on course content, etc. were polled. The survey showed that the functional aspects of training were of major concern. (Editor/LF)

Steel refining possibilities in LF

NASA Astrophysics Data System (ADS)

Dumitru, M. G.; Ioana, A.; Constantin, N.; Ciobanu, F.; Pollifroni, M.

2018-01-01

This article presents the main possibilities for steel refining in Ladle Furnace (LF). These, are presented: steelmaking stages, steel refining through argon bottom stirring, online control of the bottom stirring, bottom stirring diagram during LF treatment of a heat, porous plug influence over the argon stirring, bottom stirring porous plug, analysis of porous plugs disposal on ladle bottom surface, bottom stirring simulation with ANSYS, bottom stirring simulation with Autodesk CFD.

The analysis of soil characteristics near the animal feed and fertiliser mill using the Bartington

NASA Astrophysics Data System (ADS)

Azhari, Adinda Syifa; Agustine, Eleonora; Fitriani, Dini

2017-07-01

Industrial activities have the potential to make pollution in agricultural land, the waste contains poisonous material and it is dangerous for the environment. In general, waste from factory is dumped directly into the river, but in the current study an object that is going to be conscientious is soil on around mill. There are three sampling sites are around fertilizer plants, feed mills and original uncontaminated soil. This research has been conducted to assess the impact of pollution resulting from the two mills for the environment. Physical parameter that used is magnetic susceptibility. Sampling was conducted using the method of magnetic susceptibility of rock to see the value of low frequency (lf) and shows Frequency Dependent (fd%) using the MS2B Bartington. The results from this study is at a location close to the fertilizer plant at a depth of 0-5 cm has a value susceptibility low frequency ( lf)=187.1 - 494.8, fd (%)=1.37 - 2:46, at a depth of 6-10 cm susceptibility value of low frequency (lf)=211 - 832.7,fd (%)=1.04 - 5.37. Results in the area of animal feed mill at a depth of 0-5 cm value susceptibility low frequency (lf)=111.9 - 325.7, fd (%)=0.8 - 3.57, at a depth of 6-10 cm value susceptibility low frequency (lf)=189.2 to 386.8,fd (%)=0.33 - 3.7. Results in the original soil at a depth of 0-5 cm susceptibility value of low frequency (lf)=1188.7 - 2237.8,fd (%)=2.75 - 4.65, at a depth of 6-10 cm value susceptibility low frequency (lf)=977.7 - 2134.7,fd (%)=3.06 - 6.21. The highest value was in the arealf original, shows the area has a high mineral content andlf lows were in the area near the factory fodder it is caused by high pollution, resulting in lower mineral content in the soil.

A source migration of low frequency earthquakes during the 2000 activity of Miyake-jima volcano, Japan

NASA Astrophysics Data System (ADS)

Kobayashi, T.; Ohminato, T.; Fujita, E.; Ida, Y.

2002-12-01

The volcanic activity of Miyake-jima started at 18:30 (JST) on June 26, 2000 with large ground deformation and earthquake swarms. The seismic activity started at the southern part of the island. The hypocenter distribution migrated northwestward and slipped away out of the island by early in the morning, June 27. Low frequency (LF) earthquakes with dominant frequencies of 0.2 and 0.4 Hz were first observed in the afternoon of June 27. The LF activity lasted till the first summit eruption on July 8. Earthquake Research Institute of Tokyo University and National Research Institute for Earth Science and Disaster Prevention deployed 3 CMG-3T and 4 STS-2 broadband seismometers in the island. More than 300 LF earthquakes are detected during the period from June 27 to July 8. Most of the LF events whose dominant frequency is 0.2Hz occurred before July 1, while LF events with dominant frequency of 0.4Hz mainly occurred after July 2. We determine hypocenters of these LF events by using the following technique. For each LF event, we assume a source location on a grid point in a homogeneous half-space. A reference station is chosen among all the stations. The cross correlation coefficients are computed between the waveform of the reference station and those of other stations. Then, the coefficients for all the stations are summed. In the same manner, summations of the coefficients are computed grid by grid. A grid point that gives the maximum value of the sum of the coefficients is regarded as the best estimate of the source location of the LF event under consideration. The result shows that hypocenters of LF events are spread over the southern to western part of the island and they migrate from south to the west day by day. Hypocenter migrations associated with volcanic activity have been often reported but usually for short period events. This is one of remarkable cases in which a migration of earthquakes with dominant frequencies as low as 0.2 and 0.4Hz are clearly observed.

The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

PubMed

Pontier-Bres, Rodolphe; Rampal, Patrick; Peyron, Jean-François; Munro, Patrick; Lemichez, Emmanuel; Czerucka, Dorota

2015-10-30

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

The Saccharomyces boulardii CNCM I-745 Strain Shows Protective Effects against the B. anthracis LT Toxin

PubMed Central

Pontier-Bres, Rodolphe; Rampal, Patrick; Peyron, Jean-François; Munro, Patrick; Lemichez, Emmanuel; Czerucka, Dorota

2015-01-01

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax. PMID:26529015

Effects of a 3 strain -based direct-fed microbial and dietary fiber concentration on growth performance and expression of genes related to absorption and metabolism of volatile fatty acids in weanling pigs.

PubMed

Jaworski, N W; Owusu-Asiedu, A; Walsh, M C; McCann, J C; Loor, J J; Stein, H H

2017-01-01

Effects of a -based direct-fed microbial (DFM) on growth performance, plasma tumor necrosis factor ɑ (TNFɑ), relative gene expression, and intestinal VFA concentrations in weanling pigs fed low- or high-fiber diets were evaluated. Two hundred pigs (initial BW: 6.31 ± 0.73 kg) were allotted to 1 of 4 dietary treatments (5 pigs per pen and 10 pens per treatment). Treatments were arranged in a 2 × 2 factorial design with 2 diet types [low-fiber (LF) or high-fiber (HF)] and 2 concentrations of DFM (0 or 60 g DFM/t of feed). The DFM contained 1.5 × 10 cfu/g and was obtained from Danisco Animal Nutrition-DuPont Industrial Biosciences, Marlborough, UK. Phase 1 diets were fed for 2 wk post-weaning and phase 2 diets were fed over the following 29 d. Low fiber diets contained corn and soybean meal as main ingredients and HF diets contained corn, soybean meal, corn distillers dried grains with solubles (7.5 and 15.0% in phase 1 and 2, respectively), and wheat middlings (10.0%). Pigs and feed were weighed at the start and at the end of each phase, and ADG, ADFI, and G:F were calculated. At the conclusion of phase 2, blood was collected from 1 pig per pen and 1 pig per pen was sacrificed. Cecum and rectum contents were analyzed for VFA, and tissue samples were collected from the ileum, cecum, rectum, and liver to determine expression of genes related to absorption and metabolism of VFA using quantitative reverse transcription-PCR. Results indicated that feeding HF diets reduced ( ≤ 0.05) ADFI and ADG of pigs compared with feeding LF diets. Pigs fed DFM diets had improved ( ≤ 0.05) G:F compared with pigs fed non-DFM diets. Pigs fed LF diets had greater ( ≤ 0.05) BW at the end of phase 2 compared with pigs fed HF diets. The concentration of VFA in rectum contents was greater ( ≤ 0.05) in pigs fed LF diets than in pigs fed HF diets. The expression of in the rectum of pigs fed HF diets was greater ( ≤ 0.05) than for pigs fed LF diets, and pigs fed DFM-containing diets had an increased ( ≤ 0.05) expression of in the liver. Pigs fed HF diets had greater ( ≤ 0.05) concentrations of urea N in plasma compared with pigs fed LF diets, but dietary fiber and DFM had no effect on plasma concentration of TNF-ɑ. In conclusion, the -based DFM improved overall G:F of weanling pigs, but pigs fed LF diets had greater final BW than pigs fed HF diets.

An Integrated Model of Emotional Problems, Beta Power of Electroencephalography, and Low Frequency of Heart Rate Variability after Childhood Trauma in a Non-Clinical Sample: A Path Analysis Study.

PubMed

Jin, Min Jin; Kim, Ji Sun; Kim, Sungkean; Hyun, Myoung Ho; Lee, Seung-Hwan

2017-01-01

Childhood trauma is known to be related to emotional problems, quantitative electroencephalography (EEG) indices, and heart rate variability (HRV) indices in adulthood, whereas directions among these factors have not been reported yet. This study aimed to evaluate pathway models in young and healthy adults: (1) one with physiological factors first and emotional problems later in adulthood as results of childhood trauma and (2) one with emotional problems first and physiological factors later. A total of 103 non-clinical volunteers were included. Self-reported psychological scales, including the Childhood Trauma Questionnaire (CTQ), State-Trait Anxiety Inventory, Beck Depression Inventory, and Affective Lability Scale were administered. For physiological evaluation, EEG record was performed during resting eyes closed condition in addition to the resting-state HRV, and the quantitative power analyses of eight EEG bands and three HRV components were calculated in the frequency domain. After a normality test, Pearson's correlation analysis to make path models and path analyses to examine them were conducted. The CTQ score was significantly correlated with depression, state and trait anxiety, affective lability, and HRV low-frequency (LF) power. LF power was associated with beta2 (18-22 Hz) power that was related to affective lability. Affective lability was associated with state anxiety, trait anxiety, and depression. Based on the correlation and the hypothesis, two models were composed: a model with pathways from CTQ score to affective lability, and a model with pathways from CTQ score to LF power. The second model showed significantly better fit than the first model (AIC model1  = 63.403 > AIC model2  = 46.003), which revealed that child trauma could affect emotion, and then physiology. The specific directions of relationships among emotions, the EEG, and HRV in adulthood after childhood trauma was discussed.

An Integrated Model of Emotional Problems, Beta Power of Electroencephalography, and Low Frequency of Heart Rate Variability after Childhood Trauma in a Non-Clinical Sample: A Path Analysis Study

PubMed Central

Jin, Min Jin; Kim, Ji Sun; Kim, Sungkean; Hyun, Myoung Ho; Lee, Seung-Hwan

2018-01-01

Childhood trauma is known to be related to emotional problems, quantitative electroencephalography (EEG) indices, and heart rate variability (HRV) indices in adulthood, whereas directions among these factors have not been reported yet. This study aimed to evaluate pathway models in young and healthy adults: (1) one with physiological factors first and emotional problems later in adulthood as results of childhood trauma and (2) one with emotional problems first and physiological factors later. A total of 103 non-clinical volunteers were included. Self-reported psychological scales, including the Childhood Trauma Questionnaire (CTQ), State–Trait Anxiety Inventory, Beck Depression Inventory, and Affective Lability Scale were administered. For physiological evaluation, EEG record was performed during resting eyes closed condition in addition to the resting-state HRV, and the quantitative power analyses of eight EEG bands and three HRV components were calculated in the frequency domain. After a normality test, Pearson’s correlation analysis to make path models and path analyses to examine them were conducted. The CTQ score was significantly correlated with depression, state and trait anxiety, affective lability, and HRV low-frequency (LF) power. LF power was associated with beta2 (18–22 Hz) power that was related to affective lability. Affective lability was associated with state anxiety, trait anxiety, and depression. Based on the correlation and the hypothesis, two models were composed: a model with pathways from CTQ score to affective lability, and a model with pathways from CTQ score to LF power. The second model showed significantly better fit than the first model (AICmodel1 = 63.403 > AICmodel2 = 46.003), which revealed that child trauma could affect emotion, and then physiology. The specific directions of relationships among emotions, the EEG, and HRV in adulthood after childhood trauma was discussed. PMID:29403401

Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, T. Jonathan; Oh, Jung Hun; Folkert, Michael R.

2014-11-01

Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system wasmore » used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.« less

Biological activity of lactoferrin-functionalized biomimetic hydroxyapatite nanocrystals

PubMed Central

Nocerino, Nunzia; Fulgione, Andrea; Iannaccone, Marco; Tomasetta, Laura; Ianniello, Flora; Martora, Francesca; Lelli, Marco; Roveri, Norberto; Capuano, Federico; Capparelli, Rosanna

2014-01-01

The emergence of bacterial strains resistant to antibiotics is a general public health problem. Progress in developing new molecules with antimicrobial properties has been made. In this study, we evaluated the biological activity of a hybrid nanocomposite composed of synthetic biomimetic hydroxyapatite surface-functionalized by lactoferrin (LF-HA). We evaluated the antimicrobial, anti-inflammatory, and antioxidant properties of LF-HA and found that the composite was active against both Gram-positive and Gram-negative bacteria, and that it modulated proinflammatory and anti-inflammatory responses and enhanced antioxidant properties as compared with LF alone. These results indicate the possibility of using LF-HA as an antimicrobial system and biomimetic hydroxyapatite as a candidate for innovative biomedical applications. PMID:24623976

Ablation of porcine ligamentum flavum with Ho:YAG, q-switched Ho:YAG, and quadrupled Nd:YAG lasers.

PubMed

Johnson, Matt R; Codd, Patrick J; Hill, Westin M; Boettcher, Tara

2015-12-01

Ligamentum flavum (LF) is a tough, rubbery connective tissue providing a portion of the ligamentous stability to the spinal column, and in its hypertrophied state forms a significant compressive pathology in degenerative spinal stenosis. The interaction of lasers and this biological tissue have not been thoroughly studied. Technological advances improving endoscopic surgical access to the spinal canal makes selective removal of LF using small, flexible tools such as laser-coupled fiber optics increasingly attractive for treatment of debilitating spinal stenosis. Testing was performed to assess the effect of Ho:YAG, Q-switched Ho:YAG, and frequency quadrupled Nd:YAG lasers on samples of porcine LF. The objective was to evaluate the suitability of these lasers for surgical removal of LF. LF was resected from porcine spine within 2 hours of sacrifice and stored in saline until immediately prior to laser irradiation, which occurred within an additional 2 hours. The optical absorbance of a sample was measured over the spectral band from 190 to 2,360 nm both before and after dehydration. For the experiments using the Ho:YAG (λ = 2,080 nm, tp  = 140 µs, FWHM) and Q-Switched Ho:YAG (λ = 2,080 nm, tp  = 260 ns, FWHM) lasers, energy was delivered to the LF through a laser-fiber optic with 600 µm core and NA = 0.39. For the experiment using the frequency quadrupled Nd:YAG laser (λ = 266 nm, tp  = 5 ns FWHM), rather than applying the laser energy through a laser-fiber, the energy was focused through an aperture and lens directly onto the LF. Five experiments were conducted to evaluate the effect of the given lasers on LF. First, using the Ho:YAG laser, the single-pulse laser-hole depth versus laser fluence was measured with the laser-fiber in direct contact with the LF (1 g force) and with a standoff distance of 1 mm between the laser-fiber face and the LF. Second, with the LF remaining in situ and the spine bisected along the coronal plane, the surface temperature of the LF was measured with an IR camera during irradiation with the Ho:YAG laser, with and without constant saline flush. Third, the mass loss was measured over the course of 450 Ho:YAG pulses. Fourth, hole depth and temperature were measured over 30 pulses of fixed fluence from the Ho:YAG and Q-Switched Ho:YAG lasers. Fifth, the ablation rate and surface temperature were measured as a function of fluence from the Nd:YAG laser. Several LF staining and hole-depth measurement techniques were also explored. Aside from the expected absorbance peaks corresponding to the water in the LF, the most significant peaks in absorbance were located in the spectral band from 190 to 290 nm and persisted after the tissue was dehydrated. In the first experiment, using the Ho:YAG laser and with the laser-fiber in direct contact with the LF, the lowest single-pulse fluence for which LF was visibly removed was 35 J/cm(2) . Testing was conducted at 6 fluences between 35 and 354 J/cm(2) . Over this range the single-pulse hole depth was shown to be near linear (R(2)  = 0.9374, M = 1.6), ranging from 40 to 639 µm (N = 3). For the case where the laser-fiber face was displaced 1 mm from the LF surface, the lowest single-pulse fluence for which tissue was visibly removed was 72 J/cm(2) . Testing was conducted at 4 energy densities between 72 and 180 J/cm(2) . Over this range the single-pulse hole depth was shown to be near linear (R(2)  = 0.8951, M = 1.4), ranging from 31 to 220 µm (N = 3). In the second experiment, with LF in situ, constant flushing with room temperature saline was shown to drastically reduce surface temperature during exposure to Ho:YAG at 5 Hz with the laser-fiber in direct contact with the LF. Without saline, over 1 minute of treatment with a per-pulse fluence of 141 mJ/cm(2) , the average maximum surface temperature measured 110°C. With 10 cc's of saline flushed over 1 minute and a per-pulse laser fluence of 212 mJ/cm(2) , the average maximum surface temperature was 35°C. In the third experiment, mass loss was shown to be linear over 450 pulses of 600 mJ from the Ho:YAG laser (212 J/cm(2) , direct contact, N = 4; 108 J/cm(2) , 1 mm standoff, N = 4). With the laser-fiber in direct contact, an average of 53 mg was removed (R(2)  = 0.996, M = 0.117) and with 1 mm laser-fiber standoff, an average of 44 mg was removed (R(2)  = 0.9988, M = 0.097). In the fourth experiment, 30 pulses of the Ho:YAG and Q-Switched Ho:YAG lasers at 1 mm standoff, and 5 Hz produced similar hole depths for the tested fluences of 9 J/cm(2) (151 and 154 µm, respectively) and 18 J/cm(2) (470 and 442 µm, respectively), though the Ho:YAG laser produced significantly more carbonization around the rim of the laser-hole. The increased carbonization was corroborated by higher measured LF temperature. In all tests with the Ho:YAG and Q-Switched Ho:YAG, an audible photo-acoustic affect coincided with the laser pulse. In the fifth experiment, with the frequency quadrupled Nd:YAG laser at 15 Hz for 450 pulses, ablation depth per pulse was shown to be linear for the fluence range of 0.18 - 0.73 J/cm(2) (R(2)  = 0.989, M = 2.4). There was no noticeable photo-acoustic effect nor charring around the rim of the laser-hole. The Ho:YAG, Q-Switched Ho:YAG, and frequency quadrupled Nd:YAG lasers were shown to remove ligamentum flavum (LF). A single pulse of the Ho:YAG laser was shown to cause tearing of the tissue and a large zone of necrosis surrounding the laser-hole. Multiple pulses of the Ho:YAG and Q-Switched Ho:YAG lasers caused charring around the rim of the laser-hole, though the extent of charring was more extensive with the Ho:YAG laser. Charring caused by the Ho:YAG laser was shown to be mitigated by continuously flushing the affected LF with saline during irradiation. The Nd:YAG laser was shown to ablate LF with no gross visible indication of thermal damage to surrounding LF. © 2015 Wiley Periodicals, Inc.

Technological Innovations of Carbon Dioxide Injection in EAF-LF Steelmaking

NASA Astrophysics Data System (ADS)

Wei, Guangsheng; Zhu, Rong; Wu, Xuetao; Dong, Kai; Yang, Lingzhi; Liu, Runzao

2018-06-01

In this study, the recent innovations and improvements in carbon dioxide (CO2) injection technologies for electric arc furnace (EAF)-ladle furnace (LF) steelmaking processes have been reviewed. The utilization of CO2 in the EAF-LF steelmaking process resulted in improved efficiency, purity and environmental impact. For example, coherent jets with CO2 and O2 mixed injection can reduce the amount of iron loss and dust generation, and submerged O2 and powder injection with CO2 in an EAF can increase the production efficiency and improve the dephosphorization and denitrification characteristics. Additionally, bottom-blowing CO2 in an EAF can strengthen molten bath stirring and improve nitrogen removal, while bottom-blowing CO2 in a LF can increase the rate of desulfurization and improve the removal of inclusions. Based on these innovations, a prospective process for the cyclic utilization of CO2 in the EAF-LF steelmaking process is introduced that is effective in mitigating greenhouse gas emissions from the steelmaking shop.

Technological Innovations of Carbon Dioxide Injection in EAF-LF Steelmaking

NASA Astrophysics Data System (ADS)

Wei, Guangsheng; Zhu, Rong; Wu, Xuetao; Dong, Kai; Yang, Lingzhi; Liu, Runzao

2018-03-01

In this study, the recent innovations and improvements in carbon dioxide (CO2) injection technologies for electric arc furnace (EAF)-ladle furnace (LF) steelmaking processes have been reviewed. The utilization of CO2 in the EAF-LF steelmaking process resulted in improved efficiency, purity and environmental impact. For example, coherent jets with CO2 and O2 mixed injection can reduce the amount of iron loss and dust generation, and submerged O2 and powder injection with CO2 in an EAF can increase the production efficiency and improve the dephosphorization and denitrification characteristics. Additionally, bottom-blowing CO2 in an EAF can strengthen molten bath stirring and improve nitrogen removal, while bottom-blowing CO2 in a LF can increase the rate of desulfurization and improve the removal of inclusions. Based on these innovations, a prospective process for the cyclic utilization of CO2 in the EAF-LF steelmaking process is introduced that is effective in mitigating greenhouse gas emissions from the steelmaking shop.

Effectiveness of Tai Chi on Cardiac Autonomic Function and Symptomatology in Women With Fibromyalgia: A Randomized Controlled Trial.

PubMed

Wong, Alexei; Figueroa, Arturo; Sanchez-Gonzalez, Marcos A; Son, Won-Mok; Chernykh, Oksana; Park, Song-Young

2018-04-01

The present study examined the effects of a 12-week Tai Chi (TC) training regimen on heart rate variability (HRV), symptomatology, muscle fitness and body composition in women with fibromyalgia. Participants were randomly assigned to either a TC training group (n = 18) or a control group (n = 19). HRV, symptomatology, muscle fitness and body composition were measured before and after 12 weeks. There were significant decreases (p < 0.05) in sympathovagal balance (LnLF/LnHF), sympathetic tone (LnLF, nLF), pain, and fatigue, and significant increases (p < 0.05) in parasympathetic tone (LnHF, nHF), strength and flexibility following TC compared with no changes after control. The changes in LnLF and LnLF/LnHF were correlated with changes in pain. There were no significant changes in HR, sleep quality and body composition after TC or control. TC may be an effective therapeutic intervention for improving sympathovagal balance, pain, fatigue, strength and flexibility in women with fibromyalgia.

Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E(-/-) mice.

PubMed

Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Park, Yong-Bok; Lee, Ki-Teak; Park, Taesun; Choi, Myung-Sook

2009-07-01

The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E(-/-) mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E(-/-) mice.

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone.

PubMed

Dahmane, A; van Griensven, J; Van Herp, M; Van den Bergh, R; Nzomukunda, Y; Prior, J; Alders, P; Jambai, A; Zachariah, R

2014-03-01

Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this 'neglected disease'.

Effect of technological treatments on bovine lactoferrin: An overview.

PubMed

Franco, Indira; Pérez, María Dolores; Conesa, Celia; Calvo, Miguel; Sánchez, Lourdes

2018-04-01

Lactoferrin (LF) is a multifunctional protein that exerts important activities in the neonate through its presence in milk, and also in other external mucosas, acting as a defense protein of innate immunity. The addition of bovine LF to infant formula and also to other functional products and cosmetics has increased during the last decades. Consequently, it is essential to know the effect that the technological processes, necessary to elaborate those products, have on LF activity. In this study, we have revised the effect of classical treatments on lactoferrin structure and activity, such as heat treatment or drying, and also of emerging technologies, like high pressure or pulsed electric field. The results of the studies included in this review indicate that LF stability is dependent on its level of iron-saturation and on the characteristics of the treatment media. Furthermore, the studies revised here reveal that the non-thermal treatments are interesting alternatives to the traditional ones, as they protect better the structure and activity of lactoferrin. It is also clear the need for research on LF encapsulation by different ways, to protect its properties before it reaches the intestine. All this knowledge would allow designing processes less harmful for LF, thus maintaining all its functionality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy

PubMed Central

Moastafa, Tarek M.; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K.; Koura, Mai Salah El-Din

2014-01-01

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into. PMID:27350986

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy.

PubMed

Moastafa, Tarek M; El-Sissy, Alaa El-Din Elsayed; El-Saeed, Gehan K; Koura, Mai Salah El-Din

2014-01-01

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into.

Effect of exercise and caloric restriction on DMBA induced mammary tumorigenesis and plasma lipids in rats fed high fat diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magrane, D.

1991-03-15

Female Sprague-Dawley rats were given a single 10 mg dose of 7, 12-Dimethylbenz(a)anthracene (DMBA) and grouped as follows: (1) low fat-sedentary (LF-SED), (2) low fat-exercised (LF-EX), (3) high fat-sedentary (HF-SED), (4) high fat-exercised (HF-EX), (5) high fat-caloric restricted (HF-RES). Diets were isocaloric and contained 3.9% (LF) and 19.4% (HF) of corn oil. Group 5 was fed a 25% caloric restricted diet but with 24.6% fat content to equalize fat intake to HF-SED. After 12 weeks of diet or treadmill exercise, tumor data and plasma lipid profiles were determined. Results show that rats on HF-EX had more total tumors, % ofmore » tumors and tumors per tumor bearing rat than rats on HF-SED. The effect of exercise was also evident in LF-EX rats, when compared to LF-SED. Average tumor size and tumor volumes were not affected. The HF-RES group showed reduced tumor profiles compared to HF-SED. HDL, LDL, triglycerides and total cholesterol were unaffected by HF or LF diets or exercise. These data suggest that tumorigenesis is increased by moderate and constant exercise.« less

Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation.

PubMed

Sessa, Rosa; Di Pietro, Marisa; Filardo, Simone; Bressan, Alessia; Rosa, Luigi; Cutone, Antimo; Frioni, Alessandra; Berlutti, Francesca; Paesano, Rosalba; Valenti, Piera

2017-02-01

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

Activation of the classical pathway of complement by binding of bovine lactoferrin to unencapsulated Streptococcus agalactiae.

PubMed Central

Rainard, P

1993-01-01

The ability of lactoferrin (Lf) bound to Streptococcus agalactiae to interfere with the deposition of complement components on the bacterial surface was investigated by enzyme-linked immunosorbent assay (ELISA). By using a strain of S. agalactiae which activates the alternative pathway of complement in the absence of antibodies, it was found that pretreatment of bacteria with Lf shortened the lag phase preceding the deposition of C3 on bacteria. The kinetics of C3 deposition was comparable to that obtained by adding antibodies against S. agalactiae to agammaglobulinaemic precolostral calf serum (PCS) heated at 56 degrees for 3 min to inactivate the alternative pathway. Accelerated C3 deposition did not occur in the absence of Ca2+ ions. Deposition of C4 on bacteria occurred only when either antibodies or Lf were added to PCS. These results demonstrate that the interaction of lactoferrin with bacteria activated the classical pathway of complement in the absence of antibodies. The binding of purified C1q to bacteria was promoted in a dose-dependent manner by Lf, suggesting that recruitment of classical pathway of complement resulted from the interaction of C1q with Lf adsorbed to the bacterial surface. Phagocytosis of bacteria opsonized with heated PCS (at 56 degrees for 3 min) and Lf was comparable to that occurring in the presence of heated PCS and antibodies. In conclusion, Lf was able to substitute for antibodies in order to activate the classical pathway of complement and to opsonize unencapsulated S. agalactiae efficiently. PMID:8406591

Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains.

PubMed

Morici, P; Florio, W; Rizzato, C; Ghelardi, E; Tavanti, A; Rossolini, G M; Lupetti, A

2017-10-01

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1-11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1-11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1-11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1-11 and colistin are not strictly associated, and suggest an hLF1-11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1-11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.

The use of subionospheric VLF/LF propagation for the study of lower ionospheric perturbations associated with earthquakes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayakawa, M.

It is recently recognized that the ionosphere is very sensitive to seismic effects, and the detection of ionospheric perturbations associated with earthquakes (EQs), attracts a lot of attention as a very promising candidate for short-term EQ prediction. In this review we propose a possible use of VLF/LF (very low frequency (3-30 kHz)/low frequency (30-300 kHz)) radio sounding of seismo-ionospheric perturbations. We first present the first convincing evidence on the presence of ionospheric perturbations for the disastrous Kobe EQ in 1995. The significant shift in terminator times in the VLF/LF diurnal variation, is successfully interpreted in terms of lowering of themore » lower ionosphere prior to the EQ, which is the confirmation of seismo-ionospheric perturbations. In order to avoid the overlapping with my own previous reviews [1, 2], we try to present the latest results including the statistical evidence on the correlation between the VLF/LF propagation anomalies (ionospheric perturbations) and EQs (especially with large magnitude and with shallow depth), a case study on the Indonesia Sumatra EQ (wavelike structures in the VLF/LF data), medium-distance (6{approx}8 Mm) propagation anomalies, the fluctuation spectra of subionospheric VLF/LF data (atmospheric gravity waves effect, the effect of Earth's tides etc.), and the mechanism of lithosphere - atmosphere - ionosphere coupling. Finally, we indicate the present situation of this kind of VLF/LF activities going on in different parts of the globe and we suggest the importance of international collaboration in this seismo-electromagnetics study.« less

Influence of bovine lactoferrin on the growth of selected probiotic bacteria under aerobic conditions.

PubMed

Chen, Po-Wen; Ku, Yu-We; Chu, Fang-Yi

2014-10-01

Bovine lactoferrin (bLf) is a natural glycoprotein, and it shows broad-spectrum antimicrobial activity. However, reports on the influences of bLf on probiotic bacteria have been mixed. We examined the effects of apo-bLf (between 0.25 and 128 mg/mL) on both aerobic and anaerobic cultures of probiotics. We found that bLf had similar effects on the growth of probiotics under aerobic or anaerobic conditions, and that it actively and significantly (at concentrations of >0.25 mg/mL) retarded the growth rate of Bifidobacterium bifidum (ATCC 29521), B. longum (ATCC 15707), B. lactis (BCRC 17394), B. infantis (ATCC 15697), Lactobacillus reuteri (ATCC 23272), L. rhamnosus (ATCC 53103), and L. coryniformis (ATCC 25602) in a dose-dependent manner. Otherwise, minimal inhibitory concentrations (MICs) were 128 or >128 mg/mL against B. bifidum, B. longum, B. lactis, L. reuteri, and L. rhamnosus (ATCC 53103). With regard to MICs, bLf showed at least four-fold lower inhibitory effect on probiotics than on pathogens. Intriguingly, bLf (>0.25 mg/mL) significantly enhanced the growth of Rhamnosus (ATCC 7469) and L. acidophilus (BCRC 14065) by approximately 40-200 %, during their late periods of growth. Supernatants produced from aerobic but not anaerobic cultures of L. acidophilus reduced the growth of Escherichia coli by about 20 %. Thus, bLf displayed a dose-dependent inhibitory effect on the growth of most probiotic strains under either aerobic or anaerobic conditions. An antibacterial supernatant prepared from the aerobic cultures may have significant practical use.

Testing the tripartite model in young adolescents: is hyperarousal specific for anxiety and not depression?

PubMed

Greaves-Lord, Kirstin; Ferdinand, Robert F; Sondeijker, Frouke E P L; Dietrich, Andrea; Oldehinkel, Albertine J; Rosmalen, Judith G M; Ormel, Johan; Verhulst, Frank C

2007-09-01

To clarify the distinction between anxiety and depression, the tripartite model was introduced. According to this model, physiological hyperarousal (PH, i.e. autonomic hyperactivity) is specific for anxiety and not depression. Research on the relation between anxiety, depression and physiological measures representing arousal is lacking. Parent- and self-reported anxiety and depressive problems were assessed using the CBCL and RCADS. Heart rate (HR), heart rate variability in the low frequency (HRV LF) and respiratory sinus arrythmia (RSA) were used as indices for autonomic arousal. Parent-reported anxiety was associated with low RSA in supine posture. This association was also found for self-reported anxiety problems, but only in boys. These findings point towards high arousal in anxiety. Self-reported depressive problems were associated with low HRV LF in standing posture and high RSA in supine posture in boys, pointing towards low arousal in depression. However, self-reported depressive problems were also associated with high HR in standing posture and with low HRV LF in supine posture in girls, suggesting high arousal in depression. Although HRV LF in standing posture is primarily sympathetically mediated, and HRV LF in supine posture is primarily vagally mediated, the association between HRV LF and sympathetic versus vagal function is not exclusive. Thus, HRV LF measures are merely approaches of high or low arousal. Some evidence was found for hyperarousal in anxiety, but also for hyperarousal in depression. Apparently, the idea of hyperarousal in anxiety and not in depression is too simple to reflect the more complex reality.

Impact of humic acid on the degradation of levofloxacin by aqueous permanganate: Kinetics and mechanism.

PubMed

Xu, Ke; Ben, Weiwei; Ling, Wencui; Zhang, Yu; Qu, Jiuhui; Qiang, Zhimin

2017-10-15

Levofloxacin (LF) is a frequently detected fluoroquinolone in surface water, and permanganate (MnO 4 - ) is a commonly used oxidant in drinking water treatment. This study investigated the impact of humic acid (HA) on LF degradation by aqueous MnO 4 - from both kinetic and mechanistic aspects. In the absence of HA, the second-order rate constant (k) of LF degradation by MnO 4 - was determined to be 3.9 M -1  s -1 at pH 7.5, which increased with decreasing pH. In the presence of HA, the pseudo-first-order rate constant (k obs ) of LF degradation at pH 7.5 was significantly increased by 3.8- and 2.8-fold at [HA] o :[KMnO 4 ] o (mass ratio) = 0.5 and 1, respectively. Secondary oxidant scavenging and electron paramagnetic resonance tests indicated that HA could form a complex with Mn(III), a strongly oxidative intermediate produced in the reaction of MnO 4 - with HA, to induce the successive formation of superoxide radicals (O 2 - ) and hydroxyl radicals (OH). The resulting OH primarily contributed to the accelerated LF degradation, and the complex [HA-Mn(III)] could account for the rest of acceleration. The degradation of LF and its byproducts during MnO 4 - oxidation was mainly through hydroxylation, dehydrogenation and carboxylation, and the presence of HA led to a stronger destruction of LF. This study helps better understand the degradation of organic micropollutants by MnO 4 - in drinking water treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet.

PubMed

Legendre, Ariadne; Papakonstantinou, Emilia; Roy, Marie-Claude; Richard, Denis; Harris, Ruth B S

2007-09-01

We previously reported an exaggerated endocrine and weight loss response to stress in rats fed a high-fat (HF) diet for 5 days. Others report blunted stress-induced anxiety in rats made obese on a HF diet. Experiments described here tested whether sensitivity to stress-related peptides was changed in obese and nonobese HF-fed rats. Third ventricle infusion of corticotropin-releasing factor (CRF) in rats made obese on HF diet (40% kcal fat) produced an exaggerated hypophagia, which is thought to be mediated by CRF(2) receptors. Obese rats responded to a lower dose of CRF for a longer time than rats fed a low-fat (LF) diet (12% kcal fat). CRF-induced release of corticosterone, which is thought to be mediated by CRF(1) receptors, was not exaggerated in obese HF-fed rats. In contrast, rats fed HF diet for 5 days showed the same food intake and corticosterone response to CRF as LF-fed rats. CRF mRNA expression in the paraventricular nucleus of the hypothalamus was stimulated by mild stress (ip saline injection and placement in a novel cage) in LF-fed rats but not in rats fed HF diet for 5 days because of a nonsignificant increase in expression in nonstressed HF-fed rats. In addition, nonstressed levels of urocortin (UCN) I mRNA expression in the Edinger-Westphal nucleus were significantly inhibited in HF-fed rats. These data suggest that rats that have become obese on a HF diet show a change in responsiveness to stress peptides, whereas the increased stress response in nonobese HF-fed rats may be associated with changes in basal CRF and UCN I mRNA expression.

A high-protein low-fat diet is more effective in improving blood pressure and triglycerides in calorie-restricted obese individuals with newly diagnosed type 2 diabetes.

PubMed

Papakonstantinou, E; Triantafillidou, D; Panagiotakos, D B; Koutsovasilis, A; Saliaris, M; Manolis, A; Melidonis, A; Zampelas, A

2010-06-01

There is controversy over dietary protein's effects on cardiovascular disease risk factors in diabetic subjects. It is unclear whether observed effects are due to increased protein or reduced carbohydrate content of the consumed diets. The aim of this study was to compare the effects of two diets differing in protein to fat ratios on cardiovascular disease risk factors. A total of 17 obese (body mass index (BMI) ranging from 31 to 45 kg/m(2)) volunteers with type 2 diabetes (DM2), aged 46+/-3 years, consumed two diets, each for 4 weeks, with 3 weeks of washout period in a random, blind, crossover design. The diets were: (1) a high-protein low-fat diet (HP-LF, with 30% protein, 50% carbohydrates and 20% fat) and (2) a low-protein high-fat diet (LP-HF, with 15% protein, 50% carbohydrates and 35% fat). Their effects on fasting glycemic control, lipid levels and blood pressure, and on postprandial glucose and insulin responses after a standard test meal at the beginning and end of each dietary intervention were analyzed. Both diets were equally effective in promoting weight loss and fat loss and in improving fasting glycemic control, total cholesterol and low-density lipoprotein (LDL) cholesterol, but the HP-LF diet decreased to a greater extent triglyceride (TG) levels (P=0.04) when compared with the LP-HF diet. HP-LF diet improved significantly both systolic and diastolic blood pressure when compared with the LP-HF diet (P<0.001 and P<0.001, respectively). No differences were observed in postprandial glucose and insulin responses. A protein to fat ratio of 1.5 in diets significantly improves blood pressure and TG concentrations in obese individuals with DM2.

Enhancing physicochemical properties of emulsions by heteroaggregation of oppositely charged lactoferrin coated lutein droplets and whey protein isolate coated DHA droplets.

PubMed

Li, Xin; Wang, Xu; Xu, Duoxia; Cao, Yanping; Wang, Shaojia; Wang, Bei; Sun, Baoguo; Yuan, Fang; Gao, Yanxiang

2018-01-15

The formation and physicochemical stability of mixed functional components (lutein & DHA) emulsions through heteroaggregation were studied. It was formed by controlled heteroaggregation of oppositely charged lutein and DHA droplets coated by cationic lactoferrin (LF) and anionic whey protein isolate (WPI), respectively. Heteroaggregation was induced by mixing the oppositely charged LF-lutein and WPI-DHA emulsions together at pH 6.0. Droplet size, zeta-potential, transmission-physical stability, microrheological behavior and microstructure of the heteroaggregates formed were measured as a function of LF-lutein to WPI-DHA droplet ratio. Lutein degradation and DHA oxidation by measurement of lipid hydroperoxides and thiobarbituric acid reactive substances were determined. Upon mixing the two types of bioactive compounds droplets together, it was found that the largest aggregates and highest physical stability occurred at a droplet ratio of 40% LF-lutein droplets to 60% WPI-DHA droplets. Heteroaggregates formation altered the microrheological properties of the mixed emulsions mainly by the special network structure of the droplets. When LF-coated lutein droplets ratios were more than 30% and less than 60%, the mixed emulsions exhibited distinct decreases in the Mean Square Displacement, which indicated that their limited scope of Brownian motion and stable structure. Mixed emulsions with LF-lutein/WPI-DHA droplets ratio of 4:6 exhibited Macroscopic Viscosity Index with 13 times and Elasticity Index with 3 times of magnitudes higher than the individual emulsions from which they were prepared. Compared with the WPI-DHA emulsion or LF-lutein emulsion, the oxidative stability of the heteroaggregate of LF-lutein/WPI-DHA emulsions was improved. Heteroaggregates formed by oppositely charged bioactive compounds droplets may be useful for creating specific food structures that lead to desirable physicochemical properties, such as microrheological property, physical and chemical stabilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Music induces different cardiac autonomic arousal effects in young and older persons.

PubMed

Hilz, Max J; Stadler, Peter; Gryc, Thomas; Nath, Juliane; Habib-Romstoeck, Leila; Stemper, Brigitte; Buechner, Susanne; Wong, Samuel; Koehn, Julia

2014-07-01

Autonomic arousal-responses to emotional stimuli change with age. Age-dependent autonomic responses to music-onset are undetermined. To determine whether cardiovascular-autonomic responses to "relaxing" or "aggressive" music differ between young and older healthy listeners. In ten young (22.8±1.7 years) and 10 older volunteers (61.7±7.7 years), we monitored respiration (RESP), RR-intervals (RRI), and systolic and diastolic blood pressure (BPsys, BPdia) during silence and 180second presentations of two "relaxing" and two "aggressive" classical-music excerpts. Between both groups, we compared RESP, RRI, BPs, spectral-powers of mainly sympathetic low-frequency (LF: 0.04-0.15Hz) and parasympathetic high-frequency (HF: 0.15-0.5Hz) RRI-oscillations, RRI-LF/HF-ratios, RRI-total-powers (TP-RRI), and BP-LF-powers during 30s of silence, 30s of music-onset, and the remaining 150s of music presentation (analysis-of-variance and post-hoc analysis; significance: p<0.05). During silence, both groups had similar RRI, LF/HF-ratios and LF-BPs; RESP, LF-RRI, HF-RRI, and TP-RRI were lower, but BPs were higher in older than younger participants. During music-onset, "relaxing" music decreased RRI in older and increased BPsys in younger participants, while "aggressive" music decreased RRI and increased BPsys, LF-RRI, LF/HF-ratios, and TP-RRI in older, but increased BPsys and RESP and decreased HF-RRI and TP-RRI in younger participants. Signals did not differ between groups during the last 150s of music presentation. During silence, autonomic modulation was lower - but showed sympathetic predominance - in older than younger persons. Responses to music-onset, particularly "aggressive" music, reflect more of an arousal- than an emotional-response to music valence, with age-specific shifts of sympathetic-parasympathetic balance mediated by parasympathetic withdrawal in younger and by sympathetic activation in older participants. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of slow breathing rate on heart rate variability and arterial baroreflex sensitivity in essential hypertension.

PubMed

Li, Changjun; Chang, Qinghua; Zhang, Jia; Chai, Wenshu

2018-05-01

This study is to investigate the effects of slow breathing on heart rate variability (HRV) and arterial baroreflex sensitivity in essential hypertension.We studied 60 patients with essential hypertension and 60 healthy controls. All subjects underwent controlled breathing at 8 and 16 breaths per minute. Electrocardiogram, respiratory, and blood pressure signals were recorded simultaneously. We studied effects of slow breathing on heart rate, blood pressure and respiratory peak, high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio of HRV with traditional and corrected spectral analysis. Besides, we tested whether slow breathing was capable of modifying baroreflex sensitivity in hypertensive subjects.Slow breathing, compared with 16 breaths per minute, decreased the heart rate and blood pressure (all P < .05), and shifted respiratory peak toward left (P < .05). Compared to 16 breaths/minute, traditional spectral analysis showed increased LF power and LF/HF ratio, decreased HF power of HRV at 8 breaths per minute (P < .05). As breathing rate decreased, corrected spectral analysis showed increased HF power, decreased LF power, LF/HF ratio of HRV (P < .05). Compared to controls, resting baroreflex sensitivity decreased in hypertensive subjects. Slow breathing increased baroreflex sensitivity in hypertensive subjects (from 59.48 ± 6.39 to 78.93 ± 5.04 ms/mm Hg, P < .05) and controls (from 88.49 ± 6.01 to 112.91 ± 7.29 ms/mm Hg, P < .05).Slow breathing can increase HF power and decrease LF power and LF/HF ratio in essential hypertension. Besides, slow breathing increased baroreflex sensitivity in hypertensive subjects. These demonstrate slow breathing is indeed capable of shifting sympatho-vagal balance toward vagal activities and increasing baroreflex sensitivity, suggesting a safe, therapeutic approach for essential hypertension.

Low-gradient aortic stenosis.

PubMed

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-09-07

An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Differences in energy expenditure and substrate oxidation between habitual high fat and low fat consumers (phenotypes).

PubMed

Cooling, J; Blundell, J

1998-07-01

To investigate physiological differences between habitual high-fat (HF) and low-fat (LF) consumers, which could influence the balance between energy expenditure and energy intake, and the potential for weight gain. 16 young, lean males (eight HF and eight LF consumers; % energy from fat 44.3 and 32.0, respectively). Habitual dietary variables (from FFQ), body mass index (BMI), body fat % (measured by impedance), resting metabolic rate (RMR) (indirect calorimetry), substrate oxidation and basal heart rate, postprandial thermogenesis and heart rate in response to a high-fat (low carbohydrate (CHO)) and high-CHO (low fat) challenge. HF and LF (selected for their intake of fat) did not differ significantly in BMI or % body fat. HF had a significantly higher RMR (1624 vs 1455 kcal/d) and basal heart rate (66 vs 57 bpm) than LF. Differences in oxygen utilisation and heart rate were maintained over a 180 min period, following the high-fat and high-CHO challenge meals. HF had a significantly lower resting respiratory quotient (RQ) than LF and the differences in average RQ were significant over the 180 min examination period. HF had a significantly lower RQ response to the high fat (low CHO) than to the high CHO (low fat) challenge; this effect was not observed in LF. HF had higher total energy intake than LF and a higher absolute (but not %) intake of protein. Significant differences in basal energy expenditure and fat oxidation between habitual HF and LF consumers have been observed. The contributions of energy intake and protein intake (g not %) remain to be determined. In this particular group of subjects (young adult males) a high energy intake characterised by a large fat component is associated with metabolic adaptations which could offset the weight inducing properties of a high-fat diet. These physiological differences may be important when considering the relationship between dietary-fat and obesity.

Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival.

PubMed

Eleid, Mackram F; Sorajja, Paul; Michelena, Hector I; Malouf, Joseph F; Scott, Christopher G; Pellikka, Patricia A

2013-10-15

Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m(2) [low flow, LF] versus ≥35 mL/m(2) [normal flow, NF]) and aortic gradient (<40 mm Hg [LG] versus ≥40 mm Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71-6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25-0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG. NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.

Recombinase Polymerase Amplification Combined with Lateral Flow Strip for Listeria monocytogenes Detection in Food.

PubMed

Du, Xin-Jun; Zang, Yu-Xuan; Liu, Hai-Bin; Li, Ping; Wang, Shuo

2018-04-01

Listeria monocytogenes is an important food-borne pathogenic bacterium that causes human disease, resulting in economic losses worldwide. The current detection methods for L. monocytogenes are not well suited for direct field testing because they involve complicated, time-consuming operations. A simple, efficient method is vital for L. monocytogenes detection. In this study, we combined isothermal recombinase polymerase amplification (RPA) with a lateral flow (LF) strip to rapidly and reliably detect L. monocytogenes. In the presence of biotin- and digoxin-modified primers, RPA produced numerous digoxin- and biotin-attached duplex DNA products. These products were detected on an LF strip via dual immunoreactions (digoxin on the duplex DNA reacted with the anti-digoxin antibody on the gold nanoparticle (Au-NP) and the biotin on the duplex DNA captured by the streptavidin on the LF test zone). The accumulation of Au-NPs produced characteristic bands, enabling the visual detection of L. monocytogenes without instrumentation. This assay could be used to detect L. monocytogenes within 15 min, including DNA amplification with RPA for 10 min at 39 °C and visualization of the amplicons by LF strips for 5 min. Experiments confirmed a detection limit as low as 300 fg of DNA and 1.5 × 10 1 CFU in pure cultures. Furthermore, RPA-LF exhibited no cross-reactions with pathogens. Evaluation of the method with food samples indicated that the detection limit was substantially improved to 1.5 × 10° CFU for the original bacterial content in 25 g/mL samples after enrichment for 6 hr. RPA-LF can be used as a sensitive and rapid detection technique for L. monocytogenes. Recombinase polymerase amplification (RPA) can amplify target DNA at 37 to 42 °C without a thermal cycler. Lateral flow (LF) strips are portable, cheap and easy to operate. RPA combined with LF strips to detect Listeria monocytogenes can be widely used in remote areas. © 2018 Institute of Food Technologists®.

Assessment of lymphatic filariasis prior to re-starting mass drug administration campaigns in coastal Kenya.

PubMed

Njenga, Sammy M; Kanyi, Henry M; Mutungi, Faith M; Okoyo, Collins; Matendechero, Hadley S; Pullan, Rachel L; Halliday, Katherine E; Brooker, Simon J; Wamae, C Njeri; Onsongo, Joyce K; Won, Kimberly Y

2017-02-22

Lymphatic filariasis (LF) is a debilitating disease associated with extensive disfigurement and is one of a diverse group of diseases referred to as neglected tropical diseases (NTDs) which mainly occur among the poorest populations. In line with global recommendations to eliminate LF, Kenya launched its LF elimination programme in 2002 with the aim to implement annual mass drug administration (MDA) in order to interrupt LF transmission. However, the programme faced financial and administrative challenges over the years such that sustained annual MDA was not possible. Recently, there has been renewed interest to eliminate LF and the Kenyan Ministry of Health, through support from World Health Organization (WHO), restarted annual MDA in 2015. The objective of this study was to evaluate the current status of LF infection in the endemic coastal region of Kenya before MDA campaigns were restarted. Ten sentinel sites in Kwale, Kilifi, Tana River, Lamu, and Taita-Taveta counties in coastal Kenya were selected for participation in a cross-sectional survey of LF infection prevalence. At least 300 individuals in each sentinel village were sampled through random house-to-house visits. During the day, the point-of-care immunochromatographic test (ICT) was used to detect the presence of Wuchereria bancrofti circulating filarial antigen in finger prick blood samples collected from residents of the selected sentinel villages. Those individuals who tested positive with the ICT test were requested to provide a night-time blood sample for microfilariae (MF) examination. The overall prevalence of filarial antigenaemia was 1.3% (95% CI: 0.9-1.8%). Ndau Island in Lamu County had the highest prevalence (6.3%; 95% CI: 4.1-9.7%), whereas sites in Kilifi and Kwale counties had prevalences < 1.7%. Mean microfilarial density was also higher in Ndau Island (234 MF/ml) compared to sentinel sites in Kwale and Kilifi counties (< 25 MF/ml). No LF infection was detected in Tana River and Taita-Taveta counties. Overall, more than 88% of the study participants reported to have used a bed net the previous night. Prevalence of LF infection is generally very low in coastal Kenya, but there remain areas that require further rounds of MDA if the disease is to be eliminated as a public health problem in line with the ongoing global elimination efforts. However, areas where there was no evidence of LF transmission should be considered for WHO-recommended transmission assessment surveys in view of stopping MDA.

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

PubMed Central

Hua, Hongchen; Jiang, Ying; Wang, Yiyun; Mu, Hongjie; Wu, Zimei

2018-01-01

Background Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD). Purpose To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods HupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry. Results Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively. Conclusion Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier. PMID:29440896

Recalibrated Equations for Determining Effect of Oil Filtration on Rolling Bearing Life

NASA Technical Reports Server (NTRS)

Needelman, William M.; Zaretsky, Erwin V.

2014-01-01

In 1991, Needelman and Zaretsky presented a set of empirically derived equations for bearing fatigue life (adjustment) factors (LFs) as a function of oil filter ratings. These equations for life factors were incorporated into the reference book, "STLE Life Factors for Rolling Bearings." These equations were normalized (LF = 1) to a 10-micrometer filter rating at Beta(sub x) = 200 (normal cleanliness) as it was then defined. Over the past 20 years, these life factors based on oil filtration have been used in conjunction with ANSI/ABMA standards and bearing computer codes to predict rolling bearing life. Also, additional experimental studies have been made by other investigators into the relationship between rolling bearing life and the size, number, and type of particle contamination. During this time period filter ratings have also been revised and improved, and they now use particle counting calibrated to a new National Institute of Standards and Technology (NIST) reference material, NIST SRM 2806, 1997. This paper reviews the relevant bearing life studies and describes the new filter ratings. New filter ratings, Beta(sub x(c)) = 200 and Beta(sub x(c)) = 1000, are benchmarked to old filter ratings, Beta(sub x) = 200, and vice versa. Two separate sets of filter LF values were derived based on the new filter ratings for roller bearings and ball bearings, respectively. Filter LFs can be calculated for the new filter ratings.

EVALUATING THE PREDICTIVE VALIDITY OF SUICIDAL INTENT AND MEDICAL LETHALITY IN YOUTH

PubMed Central

Sapyta, Jeffrey; Goldston, David B.; Erkanli, Alaattin; Daniel, Stephanie S.; Heilbron, Nicole; Mayfield, Andrew; Treadway, S. Lyn

2012-01-01

Objectives To examine whether suicidal intent and medical lethality of past suicide attempts are predictive of future attempts, the association between intent and lethality, and the consistency of these characteristics across repeated attempts among youth. Method Suicide attempts in a 15-year prospective study of 180 formerly psychiatrically hospitalized adolescents (Mage at hospitalization = 14.83; 51% female; 80% Caucasian) were characterized using the Subjective Intent Rating Scale and Lethality of Attempt Rating Scale. Anderson-Gill recurrent events survival models and generalized estimating equations were used to assess predictive validity. Generalized linear models were used to examine stability of characteristics across attempts. Results Neither intent nor lethality from the most recent attempt predicted future attempts. The highest level of intent and most severe lethality of attempts during the follow-up predicted subsequent attempts, but the degree to which highest intent and most severe lethality contributed to prediction after considering methods of suicide attempts, past number of attempts, or psychiatric diagnoses was mixed. Across successive attempts, there was little consistency in reported characteristics. Intent and lethality were related to each other only for attempts occurring in early adulthood. Conclusions Highest intent and lethality were better predictors of future attempts than intent and lethality of the most recent attempt. However, these characteristics should only be considered as predictors within the context of other factors. For youth, clinicians should not infer true intent from the lethality of attempts, nor assume that characteristics of future suicide attempts will be similar to previous attempts. PMID:22250854

Organochlorine poisoning of herons

USGS Publications Warehouse

Ohlendorf, Harry M.; Swineford, Douglas M.; Locke, Louis N.; Southern, William E.

1979-01-01

Over a period of years interested individuals have submitted many dead or moribund herons of various species to our laboratory to learn whether the birds had been affected by diseases or organochlorine poisoning. Residue concentrations in carcasses of birds and mammals are considered the best measure of sublethal exposure, whereas residues in brains are best to use for diagnosing death by most organochlorine chemicals (see Heinz et al. 1979 for review). Residue concentrations in brains that are diagnostic of organochlorine poisoning for birds have been determined in the laboratory for DDT and its metabolites (L.F. Stickel et al. 1966; W.H. Stickel et al. 1970; Stickel and Stickel 1970; W.H. Stickel, pers. comm.); dieldrin (W.H. Stickel et al. 1969; W.H. Stickel, pers. comm.); heptachlor, chlordane, and oxychlordane (L.F. Stickel et al. 1979; W.H. Stickel, pers. comm.); endrin (W.H. Stickel et al. 1979); Aroclor 1254 (W.H. Stickel 1975; W.H. Stickel, pers. comm.); and mirex (W.H. Stickel et al. 1973). This subject is discussed in further detail by Heinz et al. (1979). The purpose of the present paper is to document the occurrence and concentration of organochlorine residues in the brains of herons from various areas in the United States. By comparing these residue concentrations with laboratory-determined diagnostic lethal levels, we conclude that some herons were killed by organochlorine poisoning; others were at least seriously endangered by the residues they carried. Complete results of carcass analyses for these and other herons, as well as further details on residues in brains, will be reported elsewhere (H.M. Ohlendorf, D.M. Swineford, and L.N. Locke, unpublished manuscript). Overall, we analyzed carcasses or brains of more than 70 herons found dead or moribund and 36 others taken in planned collections. Residue levels in carcasses of many herons were not high enough to warrant analysis of brains. In the present paper we compare carcass and brain residues of dieldrin in 23 herons of which both carcass and brain were analyzed.

Lethality of First Contact Dysentery Epidemics on Pacific Islands

PubMed Central

Shanks, G. Dennis

2016-01-01

Infectious diseases depopulated many isolated Pacific islands when they were first exposed to global pathogen circulation from the 18th century. Although the mortality was great, the lack of medical observers makes determination of what happened during these historical epidemics largely speculative. Bacillary dysentery caused by Shigella is the most likely infection causing some of the most lethal island epidemics. The fragmentary historical record is reviewed to gain insight into the possible causes of the extreme lethality that was observed during first-contact epidemics in the Pacific. Immune aspects of the early dysentery epidemics and postmeasles infection resulting in subacute inflammatory enteric disease suggest that epidemiologic isolation was the major lethality risk factor on Pacific islands in the 19th century. Other possible risk factors include human leukocyte antigen homogeneity from a founder effect and pathogen-induced derangement of immune tolerance to gut flora. If this analysis is correct, then Pacific islands are currently at no greater risk of emerging disease epidemics than other developing countries despite their dark history. PMID:27185765

Laboratory simulations of fluid-induced seismicity in shallow volcanic faults

NASA Astrophysics Data System (ADS)

Fazio, Marco; Benson, Philip; Vinciguerra, Sergio; Meredith, Philip

2015-04-01

Seismicity is a key tool used for monitoring fracturing and faulting in around volcanoes, with a particular emphasis placed on the frequency (Long period or Low Frequency, LF events) thought to be due to fluid movement, as compared to Volcano-Tectonic activity driven by pure fracture. To better understand these fundamental processes this research presents new rock deformation experiments designed to simulate shallow volcano-tectonic pressure/temperature conditions, linking pore fluid flow to the induced seismicity. A particular emphasis is placed on the conditions of pressure and temperature required to stimulate LF activity. Our setup imposes a rapid pore pressure release or "venting" via a small pre-drilled axial conduit to stimulate rapid fluid movement through an established fracture damage zone via a two stage process. Firstly experiments are conducted to generate a through-going shear fracture, with pore fluid connectivity to this fracture enhanced via the axial conduit. The shear failure is imaged via AE location with ~mm scale accuracy. The second stage vents pore fluid pressure via an electrical solenoid valve. We find that this second stage is accompanied by a swarm of LF activity akin to Long Period (LP) activity on active volcanoes. We find that a significant change in the dominant frequency of LF events is recorded as pore fluid pressure decrease through, and beyond, the water boiling point and the transition between LF and VLF occurred at the pressure at which the superheated water turn to vapour. In addition, we observe a significant dependence of the recorded LF upon the fluid flow rate. Finally, we present new data using low frequency (200 kHz) AE sensors, in conjunction with our standard 1 MHz-central-frequency sensors, which permit us to better constraint LF and VLF events with lower attenuation, and hence an improved characterization of these LF seismic signals. Data are used to forecast the final time of failure via the fracture forecast methods of Kilburn (2004), showing a good correlation between measured sample failure time and the forecast time based on AE event rate. Our data showed little change in forecast accuracy when using LF data compared to regular HF data, illustrating the importance of newly fracturing surfaces in the application of such models.

Laboratory simulations of fluid-induced seismicity in shallow volcanic faults

NASA Astrophysics Data System (ADS)

Fazio, M.; Benson, P. M.; Vinciguerra, S.

2014-12-01

Seismicity is a key tool used for monitoring fracturing and faulting in around volcanoes, with a particular emphasis placed on the frequency (Long period or Low Frequency, LF events) thought to be due to fluid movement, as compared to Volcano-Tectonic activity driven by pure fracture. To better understand these fundamental processes this research presents new rock deformation experiments designed to simulate shallow volcano-tectonic pressure/temperature conditions, linking pore fluid flow to the induced seismicity. A particular emphasis is placed on the conditions of pressure and temperature required to stimulate LF activity. Our setup imposes a rapid pore pressure release or "venting" via a small pre-drilled axial conduit to stimulate rapid fluid movement through an established fracture damage zone via a two stage process. Firstly experiments are conducted to generate a through-going shear fracture, with pore fluid connectivity to this fracture enhanced via the axial conduit. The shear failure is imaged via AE location with ~mm scale accuracy. The second stage vents pore fluid pressure via an electrical solenoid valve. We find that this second stage is accompanied by a swarm of LF activity akin to Long Period (LP) activity on active volcanoes. We find that a significant change in the dominant frequency of LF events is recorded as pore fluid pressure decrease through, and beyond, the water boiling point and the transition between LF and VLF occurred at the pressure at which the superheated water turn to vapour. In addition, we observe a significant dependence of the recorded LF upon the fluid flow rate. Finally, we present new data using low frequency (200 kHz) AE sensors, in conjunction with our standard 1 MHz-central-frequency sensors, which permit us to better constraint LF and VLF events with lower attenuation, and hence an improved characterization of these LF seismic signals. Data are used to forecast the final time of failure via the fracture forecast methods of Kilburn (2004), showing a good correlation between measured sample failure time and the forecast time based on AE event rate. Our data showed little change in forecast accuracy when using LF data compared to regular HF data, illustrating the importance of newly fracturing surfaces in the application of such models.

[Effects of adiponectin gene SNP45T/G on changes of serum lipid ratios induced by high-carbohydrate/low-fat diet in healthy Chinese youth].

PubMed

Li, Yu-jia; Fang, Ding-zhi; Gong, Ren-rong; Du, Juan; Huang, Xin

2010-09-01

To investigate the effects of adiponectin gene (APM1) SNP45T/G on serum lipid ratios and their responses to high-carbohydrate/low-fat (HC/LF) diet in healthy young Chinese. Fifty-six healthy young subjects were given two consecutive diets. The first was control diet (54% carbohydrate, 15% protein, and 31% fat) for 7 days, and the second was HC/LF diet (70% carbohydrate, 15% protein, and 15% fat) for 6 days. Before and after each diet, serum lipids and SNP45T/G were analyzed. The ratios of TG/HDL-C, log (TG/HDL-C), TC/HDL-C, and LDL-C/HDL-C were calculated. There was no significant difference of baseline lipid ratios between subjects with TT genotype and subjects carrying G allele (G carriers) in the whole population or in the males and females separately. The G allele was associated with significantly higher TC/HDL-C after HC/LF diet in the males (P < 0.05); and the males with TT genotype had significant decreases of LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.05) after HC/LF diet compared with those before the diet, while G carriers only experienced significant decrease of TC/HDL-C (P < 0.01). In the females, TT genotype was associated with significantly higher TG/HDL-C (P < 0.05) and log (TG/HDL-C) (P < 0.05) both before and after the HC/LF diet. When compared with those before HC/LF diet, elevated TG/HDL-C (P < 0.05) and log (TG/ HDL-C) (P < 0.05) and declined TC/HDL-C (P < 0.01) were observed in the subjects with TT genotype after the diet. In the female subjects of G carriers, LDL-C/HDL-C (P < 0.05) and TC/HDL-C (P < 0.01) decreased significantly after the HC/LF diet. G allele of APM1 45T/G could inhibit increase of TG/HDL-C and log (TG/HDL-C) and promote the decrease of LDL-C/HDL-C induced by HC/LF diet in healthy young females. But in the healthy young males, it might eliminate the decline of LDL-C/HDL-C induced by HC/LF diet and increase TC/HDL-C.

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise.

PubMed

Sun, Peng; Yan, Huimin; Ranadive, Sushant M; Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Baynard, Tracy; Hu, Min; Li, Shichang; Fernhall, Bo

2016-01-01

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R-R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese. Chinese Clinical Trial Register ChiCTR-IPR-15006684.

Autonomic Recovery Is Delayed in Chinese Compared with Caucasian following Treadmill Exercise

PubMed Central

Sun, Peng; Yan, Huimin; Ranadive, Sushant M.; Lane, Abbi D.; Kappus, Rebecca M.; Bunsawat, Kanokwan; Baynard, Tracy; Hu, Min; Li, Shichang; Fernhall, Bo

2016-01-01

Caucasian populations have a higher prevalence of cardiovascular disease (CVD) when compared with their Chinese counterparts and CVD is associated with autonomic function. It is unknown whether autonomic function during exercise recovery differs between Caucasians and Chinese. The present study investigated autonomic recovery following an acute bout of treadmill exercise in healthy Caucasians and Chinese. Sixty-two participants (30 Caucasian and 32 Chinese, 50% male) performed an acute bout of treadmill exercise at 70% of heart rate reserve. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were obtained during 5-min epochs at pre-exercise, 30-min, and 60-min post-exercise. HRV was assessed using frequency [natural logarithm of high (LnHF) and low frequency (LnLF) powers, normalized high (nHF) and low frequency (nLF) powers, and LF/HF ratio] and time domains [Root mean square of successive differences (RMSSD), natural logarithm of RMSSD (LnRMSSD) and R–R interval (RRI)]. Spontaneous BRS included both up-up and down-down sequences. At pre-exercise, no group differences were observed for any HR, HRV and BRS parameters. During exercise recovery, significant race-by-time interactions were observed for LnHF, nHF, nLF, LF/HF, LnRMSSD, RRI, HR, and BRS (up-up). The declines in LnHF, nHF, RMSSD, RRI and BRS (up-up) and the increases in LF/HF, nLF and HR were blunted in Chinese when compared to Caucasians from pre-exercise to 30-min to 60-min post-exercise. Chinese exhibited delayed autonomic recovery following an acute bout of treadmill exercise. This delayed autonomic recovery may result from greater sympathetic dominance and extended vagal withdrawal in Chinese. Trial Registration: Chinese Clinical Trial Register ChiCTR-IPR-15006684 PMID:26784109

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

Maturation of Heart Rate and Blood Pressure Variability during Sleep in Term-Born Infants

PubMed Central

Yiallourou, Stephanie R.; Sands, Scott A.; Walker, Adrian M.; Horne, Rosemary S.C.

2012-01-01

Study Objectives: Abnormal blood pressure control is implicated in the sudden infant death syndrome (SIDS). However, no data exist on normal development of blood pressure control during infancy. This study assessed maturation of autonomic control of blood pressure and heart rate during sleep within the first 6 months of life. Participants: Term infants (n = 31) were studied longitudinally at 2-4 weeks, 2-3 months, and 5-6 months postnatal age. Interventions: Infants underwent daytime polysomnography at each age studied. Blood pressure and heart rate were recorded during quiet (QS) and active (AS) sleep in undisturbed baseline and head-up tilt conditions. Measurements and Results: Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity) and high frequency (HF, parasympathetic activity), total power (LF+HF), and LF/HF ratio (sympathovagal balance). With increasing postnatal age and predominantly during QS, HRV-LF, HRV-HF, and HRV total power increased, while HRV-LF/HF decreased. BPV-LF/HF also decreased with postnatal age. All changes were evident in both baseline and head-up tilt conditions. BPV-LF and BPV total power during tilts were markedly reduced in QS versus AS at each age. Conclusions: In sleeping infants, sympathetic vascular modulation of the circulation decreases with age, while parasympathetic control of heart rate is strengthened. These normative data will aid in the early identification of conditions where autonomic function is impaired, such as in SIDS. Citation: Yiallourou SR; Sands SA; Walker AM; Horne RSC. Maturation of heart rate and blood pressure variability during sleep in term-born infants. SLEEP 2012;35(2):177-186. PMID:22294807

Preoperative depressed mood and perioperative heart rate variability in patients with hepatic cancer.

PubMed

Kim, Eun-Hee; Park, Jin-Hyoung; Lee, Sangmin M; Gwak, Mi-Sook; Kim, Gaab-Soo; Kim, Myung-Hee

2016-12-01

How perioperative heart rate variability (HRV) indices differ according to the anxiety or depressed mood of patients scheduled to undergo a major surgical procedure for cancer. Prospective observational study. Operating room. Forty-one male patients between 40 and 70 years of age with hepatocellular carcinoma were included in the final analysis. HRV was measured on the day before surgery (T1), impending anesthesia (T2), and after anesthetic induction (T3). Preoperative anxiety and depressed mood of all patients were evaluated using the State-Trait Anxiety Inventory and Self-Rating Depression Scale (SDS). HRV was significantly different among T1, T2, and T3. At T2, high frequency (HF) (normalized units of HF [nuHF]) was decreased and low frequency (LF) (normalized units of LF) and LF/HF were increased compared with those at T1 and T3. In the subgroup analysis between high and low SDS groups, high SDS group showed significantly decreased nuHF (P = .035), increased nuLF (P = .039), and increased LF/HF (P = .020) compared to low SDS group at T1. However, these values at T2 and T3 were not different between 2 groups. In analysis within the groups, low SDS group showed significant differences in nuHF, nuLF, and LF/HF among T1, T2, and T3 (P < .05, respectively), but no changes in these values were observed in high SDS group among the 3 different time points. HRV decreased significantly immediately before anesthesia and recovered to baseline with anesthetic induction. Preoperative, more depressed patients showed increased sympathetic tone at baseline and blunted response to impending anesthesia on the HRV measurements. Copyright © 2016 Elsevier Inc. All rights reserved.

Supplementing suckling rats with whey protein concentrate modulates the immune response and ameliorates rat rotavirus-induced diarrhea.

PubMed

Pérez-Cano, Francisco J; Marín-Gallén, Silvia; Castell, Margarida; Rodríguez-Palmero, María; Rivero, Montserrat; Castellote, Cristina; Franch, Angels

2008-12-01

Group A rotaviruses (RV) are the most common causative agents of acute gastroenteritis in children <2 y. The present study was designed to establish the effect of a bovine whey protein concentrate (WPC) in a RV infection model in suckling rats. From d 3 of life, suckling Lewis rats received daily supplements of WPC, WPC plus lactoferrin (LF), standard infant formula (SIF), or water (RV-infected group and an untreated, uninfected reference group). On d 8 of life, heterologous simian RV SA-11 was inoculated orally in the WPC-RV, WPC+LF-RV, SIF-RV, and RV groups. WPC and WPC+LF reduced diarrhea incidence from approximately 90% in RV group to approximately 60% in WPC-RV and WPC+LF-RV groups (P < 0.05), whereas the area under the curve (AUC) of severity along time diminished from approximately 10 AUC in the RV group to approximately 6 AUC in both supplemented groups (P < 0.05). Serum levels of anti-RV antibodies, splenocyte proliferation, and interferon-gamma secretion after specific stimulation were significantly lower in the WPC-RV and WPC+LF-RV groups than in the SIF-RV and RV groups. In the intraepithelial intestinal compartment, RV infection increased the proportion of typical mucosal T cells (IE-T CD8alphaalpha+); however, this modification was controlled by WPC and WPC+LF supplementation. In general, for most of the parameters studied, the SIF-RV and RV groups did not differ. In summary, daily supplementation with WPC or WPC+LF in early life considerably reduces the severity of RV-induced acute gastroenteritis and modulates the immune response against the pathogen.

Study on the Simultaneously Quantitative Detection for β-Lactoglobulin and Lactoferrin of Cow Milk by Using Protein Chip Technique.

PubMed

Yin, Ji Yong; Huo, Jun Sheng; Ma, Xin Xin; Sun, Jing; Huang, Jian

2017-12-01

To research a protein chip method which can simultaneously quantitative detect β-Lactoglobulin (β-L) and Lactoferrin (Lf) at one time. Protein chip printer was used to print both anti-β-L antibodies and anti-Lf antibodies on each block of protein chip. And then an improved sandwich detection method was applied while the other two detecting antibodies for the two antigens were added in the block after they were mixed. The detection conditions of the quantitative detection for simultaneous measurement of β-L and Lf with protein chip were optimized and evaluated. Based on these detected conditions, two standard curves of the two proteins were simultaneously established on one protein chip. Finally, the new detection method was evaluated by using the analysis of precision and accuracy. By comparison experiment, mouse monoclonal antibodies of the two antigens were chosen as the printing probe. The concentrations of β-L and Lf probes were 0.5 mg/mL and 0.5 mg/mL, respectively, while the titers of detection antibodies both of β-L and Lf were 1:2,000. Intra- and inter-assay variability was between 4.88% and 38.33% for all tests. The regression coefficients of protein chip comparing with ELISA for β-L and Lf were better than 0.734, and both of the two regression coefficients were statistically significant (r = 0.734, t = 2.644, P = 0.038; and r = 0.774, t = 2.998, P = 0.024). A protein chip method of simultaneously quantitative detection for β-L and Lf has been established and this method is worthy in further application. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Severe aortic stenosis patients with preserved ejection fraction according to flow and gradient classification: Prevalence and outcomes.

PubMed

González Gómez, Ariana; Fernández-Golfín, Covadonga; Monteagudo, Juan Manuel; Izurieta, Carlos; Hinojar, Rocío; García, Ana; Casas, Eduardo; Jiménez-Nacher, José Julio; Moya, José Luis; Ruiz, Soledad; Zamorano, José Luis

2017-12-01

Clinicians often encounter patients with apparently discordant echocardiographic findings, severe aortic stenosis (SAS) defined by aortic valve area (AVA) despite a low mean gradient. A new classification according to flow state and pressure gradient has been proposed. We sought to assess the prevalence, characteristics and outcomes of patients with asymptomatic SAS with preserved left-ventricular ejection fraction (LVEF) according to flow and gradient. In total 442 patients with SAS (AVAi<0.6 cm2/m2) and LVEF ≥50% (mean age 80+11years, 54,5% female) were included. Patients were classified according to flow state (≥ or <35ml/m 2 ) and mean pressure gradient (≥ or <40mmHg): Low Flow/Low Gradient (LF/LG): 21.3%(n=94); Normal Flow/Low Gradient (NF/LG): 32.1%(n=142); Low Flow/High Gradient (LF/HG): 6.8%(n=30); Normal Flow/High Gradient (NF/HG): 39,8%(n=176). Mean follow-up time was 20.5months (SD=10.3). Primary combined endpoint was cardiovascular mortality and hospital admission for SAS related symptom, secondary endpoint was aortic valve replacement (AVR), comparing HG group to LF/LG group. During follow-up 17 (18%) of LF/LG patients and 21 (10.2%) of HG patients met the primary endpoint. A lower free of event survival (cardiovascular mortality and hospital admission) was observed in patients with LF/LG AS (Breslow, p=0.002). Significant differences were noted between groups with a lower AVR free survival in the LF/LG group compared to HG groups (Breslow, p=0.002). Our study confirms the high prevalence and worse prognosis of LF/LG SAS. Clinicians must be aware of this entity to ensure appropriate patient management. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ladra, Matthew M.; Mandeville, Henry C.; Niemierko, Andrzej

2015-06-01

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results:more » With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.« less

Mechanisms of Autonomic Dysfunction Associated with Extreme Exertional Heat Stroke and Potential Efficacy of Novel Pharmacological Treatments

DTIC Science & Technology

2014-12-01

cardiovascular diseases. At higher doses, these medications have been prescribed to treat high blood pressure in humans and both may have relevance as...HR, and Tc. § Low frequency (LF) systolic blood pressure variability as an index of sympathetic modulation of vascular tone. § LF and high ... blood pressure variability (LFSYS), LF heart rate variability (LFHR), and high frequency heart rate variability (HFHR) in placebo-, clonidine-, and

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone

PubMed Central

Dahmane, A.; van Griensven, J.; Van Herp, M.; Van den Bergh, R.; Nzomukunda, Y.; Prior, J.; Alders, P.; Jambai, A.; Zachariah, R.

2014-01-01

Background Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. Methods We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). Results There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. Conclusions These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this ‘neglected disease’. PMID:24535150

Fluorescence spectroscopic detection of virus-induced atherosclerosis

NASA Astrophysics Data System (ADS)

Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

1994-07-01

Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model

PubMed Central

Heinritz, Sonja N.; Weiss, Eva; Eklund, Meike; Aumiller, Tobias; Heyer, Charlotte M.E.; Messner, Sabine; Rings, Andreas; Louis, Sandrine; Bischoff, Stephan C.; Mosenthin, Rainer

2016-01-01

To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05). Higher gene copy numbers of Bacteroides (p < 0.05) and Enterobacteriaceae (p < 0.001) were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05). Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05). Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT) showed higher concentrations upon feeding the LF diet (p < 0.001). However, C-reactive protein (CRP) decreased with time in LF pigs (p < 0.05). In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model. PMID:27223303

Structural and magnetic properties of the products of the transformation of ferrihydrite: Effect of cobalt dications

NASA Astrophysics Data System (ADS)

Camacho, K. I.; Pariona, N.; Martinez, A. I.; Baggio-Saitovitch, E.; Herrera-Trejo, M.; Perry, Dale L.

2017-05-01

The effect of cobalt dications on the transformation of 2-line ferrihydrite (2LF) has been studied. The products of the transformation reaction were characterized by X-ray diffraction, Mössbauer spectroscopy (MS), transmission electron microscopy (TEM), magnetometry, and first-order reversal curve (FORC) diagrams. It was found that the concentration of cobalt dications plays an important role on the structural and magnetic properties of the products; i.e., for low cobalt concentrations, cobalt-substituted hematite is formed, while higher concentrations promote the formation of cobalt-substituted magnetite. Structural results revealed that formation of other iron oxide polymorphs is avoided and residual 2LF is always present in the final products. In this way, hematite/2LF and magnetite/2LF nanocomposites were formed. For all the samples, magnetic measurements yielded non-saturated hysteresis loops at a maximum field of 12 kOe. For cobalt-substituted hematite/2LF samples, FORC diagrams revealed the presence of multiple single-domain (SD) components which generate interaction coupling between SD with low and high coercivity. Moreover, for cobalt-substituted magnetite/2LF samples, the FORC diagrams revealed the components of wasp-waist hysteresis loops which consist of mixtures of SD and superparamagnetic particles. One of the goals of the present study is the rigorous, experimental documentation of ferrihydrite/hematite mixtures as a function of reaction conditions for use as analytical standards research.

Effect of deep pressure input on parasympathetic system in patients with wisdom tooth surgery.

PubMed

Chen, Hsin-Yung; Yang, Hsiang; Meng, Ling-Fu; Chan, Pei-Ying Sarah; Yang, Chia-Yen; Chen, Hsin-Ming

2016-10-01

Deep pressure input is used to normalize physiological arousal due to stress. Wisdom tooth surgery is an invasive dental procedure with high stress levels, and an alleviation strategy is rarely applied during extraction. In this study, we investigated the effects of deep pressure input on autonomic responses to wisdom tooth extraction in healthy adults. A randomized, controlled, crossover design was used for dental patients who were allocated to experimental and control groups that received treatment with or without deep pressure input, respectively. Autonomic indicators, namely the heart rate (HR), percentage of low-frequency (LF) HR variability (LF-HRV), percentage of high-frequency (HF) HRV (HF-HRV), and LF/HF HRV ratio (LF/HF-HRV), were assessed at the baseline, during wisdom tooth extraction, and in the posttreatment phase. Wisdom tooth extraction caused significant autonomic parameter changes in both groups; however, differential response patterns were observed between the two groups. In particular, deep pressure input in the experimental group was associated with higher HF-HRV and lower LF/HF-HRV during extraction compared with those in the control group. LF/HF-HRV measurement revealed balanced sympathovagal activation in response to deep pressure application. The results suggest that the application of deep pressure alters the response of HF-HRV and facilitates maintaining sympathovagal balance during wisdom tooth extraction. Copyright © 2016. Published by Elsevier B.V.

Impact of a High-Fat or High-Fiber Diet on Intestinal Microbiota and Metabolic Markers in a Pig Model.

PubMed

Heinritz, Sonja N; Weiss, Eva; Eklund, Meike; Aumiller, Tobias; Heyer, Charlotte M E; Messner, Sabine; Rings, Andreas; Louis, Sandrine; Bischoff, Stephan C; Mosenthin, Rainer

2016-05-23

To further elaborate interactions between nutrition, gut microbiota and host health, an animal model to simulate changes in microbial composition and activity due to dietary changes similar to those in humans is needed. Therefore, the impact of two different diets on cecal and colonic microbial gene copies and metabolic activity, organ development and biochemical parameters in blood serum was investigated using a pig model. Four pigs were either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for seven weeks, with both diets being isocaloric. A hypotrophic effect of the HF diet on digestive organs could be observed compared to the LF diet (p < 0.05). Higher gene copy numbers of Bacteroides (p < 0.05) and Enterobacteriaceae (p < 0.001) were present in intestinal contents of HF pigs, bifidobacteria were more abundant in LF pigs (p < 0.05). Concentrations of acetate and butyrate were higher in LF pigs (p < 0.05). Glucose was higher in HF pigs, while glutamic pyruvic transaminase (GPT) showed higher concentrations upon feeding the LF diet (p < 0.001). However, C-reactive protein (CRP) decreased with time in LF pigs (p < 0.05). In part, these findings correspond to those in humans, and are in support of the concept of using the pig as human model.

Bovine Mammary Nutrigenomics and Changes in the Milk Composition due to Rapeseed or Sunflower Oil Supplementation of High-Forage or High-Concentrate Diets.

PubMed

Leroux, Christine; Bernard, Laurence; Faulconnier, Yannick; Rouel, Jacques; de la Foye, Anne; Domagalski, Jordann; Chilliard, Yves

2016-01-01

Fatty acid (FA) composition plays a crucial role in milk nutritional quality. Despite the known nutritional regulation of ruminant milk composition, the overall mammary mechanisms underlying this regulation are far from being understood. The aim of our study was to determine nutritional regulation of mammary transcriptomes in relation to the cow milk composition. Twelve cows received diets differing in the forage-to-concentrate ratio [high forage (HF) and low forage (LF)] supplemented or not with lipids [HF with whole intact rapeseeds (RS) and LF sunflower oil (SO)] in a 4 × 4 Latin square design. Milk production and FA composition were determined. The gene expression profile was studied using RT-qPCR and a bovine microarray. Our results showed a higher amplitude of milk composition and mammary transcriptome responses to lipid supplementation with the LF-SO compared with the LF diet than with the HF-RS compared with the HF diet. Forty-nine differentially expressed genes, including genes involved in lipid metabolism, were identified with LF-SO versus LF, whereas RS supplementation to the HF diet did not affect the mammary transcriptome. This study highlights different responses to lipid supplementation of milk production and composition and mammary transcriptomes depending on the nature of lipid supplementation and the percentage of dietary concentrate. © 2016 S. Karger AG, Basel.

Elevated levels of triglyceride and triglyceride-rich lipoprotein triglyceride induced by a high-carbohydrate diet is associated with polymorphisms of APOA5-1131T>C and APOC3-482C>T in Chinese healthy young adults.

PubMed

Lin, Jia; Fang, Ding Zhi; Du, Juan; Shigdar, Sarah; Xiao, Li Ying; Zhou, Xue Dong; Duan, Wei

2011-01-01

Changes in lipid profiles have been shown to be associated with diet and apolipoprotein (APO) polymorphisms. Therefore, 2 polymorphisms, i.e. APOA5-1131T>C and APOC3-482C>T, and serum lipids were examined in a Chinese healthy young population with high-carbohydrate/low-fat (HC/LF) diet intervention. After a wash-out diet for 7 days, 56 young adults (22.89 ± 1.80 years) received the HC/LF diet for 6 days. Body mass index (BMI) and fasting serum lipid profiles at baseline, after the wash-out diet, and after the HC/LF diet were measured. APOA5-1131C carriers had higher triglyceride (TG) and TG-rich lipoprotein TG (TRL-TG) levels at baseline and after the HC/LF diet, though this mainly corresponded to the female cohort. APOC3-482T carriers had higher TRL-TG levels following the wash-out and HC/LF diets, but these were not directly attributable to a single gender. Both polymorphisms may play an important role in the elevated TG and TRL-TG levels induced by the HC/LF diet, especially in females, thus indicating a potential dietary prevention of coronary heart disease in this Chinese cohort. Copyright © 2011 S. Karger AG, Basel.

CRM1 plays a nuclear role in transporting snoRNPs to nucleoli in higher eukaryotes.

PubMed

Verheggen, Celine; Bertrand, Edouard

2012-03-01

Here, we review the sn- and sno-RNA transport pathways in S. cerevisiae and humans, aiming at understanding how they evolved and how common factors can have distinct functions depending on the RNA they bind. We give a particular emphasis on Tgs1, the cap hypermethylase that is conserved from yeast to humans and appears to play a central role in both sn- and sno-RNA biogenesis. In yeast, Tgs1 hypermethylates sn- and sno-RNAs in the nucleolus. In humans, Tgs1 occurs in two forms: a long isoform (Tgs1 LF), which locates in the cytoplasm and Cajal bodies, which is predominantly associated with snRNAs and a short isoform (Tgs1 SF), which is nuclear and mainly associates with snoRNAs. We show that Tgs1 LF is exported by CRM1 and that interaction with CRM1 competes for binding with the C-terminal domain of the core protein Nop58, which contains the Nucleolar localization signal of Box C/D snoRNPs (NoLS). Our data suggest a model where CRM1 removes Tgs1 LF from snoRNPs, thereby promoting nucleolar targeting via activation of their NoLS. In this review, we argue that CRM1, while first described as an export receptor, can also control the composition of nucleoplasmic complexes. Thus, it could coordinate the fate of these complexes with the general nucleo-cytoplasmic trafficking.

An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

PubMed

Nakamura, Kentaro; Sasayama, Akina; Takahashi, Takeshi; Yamaji, Taketo

2015-01-01

Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

Rapid and automatic chemical identification of the medicinal flower buds of Lonicera plants by the benchtop and hand-held Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Jianbo; Guo, Baolin; Yan, Rui; Sun, Suqin; Zhou, Qun

2017-07-01

With the utilization of the hand-held equipment, Fourier transform infrared (FT-IR) spectroscopy is a promising analytical technique to minimize the time cost for the chemical identification of herbal materials. This research examines the feasibility of the hand-held FT-IR spectrometer for the on-site testing of herbal materials, using Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) as examples. Correlation-based linear discriminant models for LJF and LF are established based on the benchtop and hand-held FT-IR instruments. The benchtop FT-IR models can exactly recognize all articles of LJF and LF. Although a few LF articles are misjudged at the sub-class level, the hand-held FT-IR models are able to exactly discriminate LJF and LF. As a direct and label-free analytical technique, FT-IR spectroscopy has great potential in the rapid and automatic chemical identification of herbal materials either in laboratories or in fields. This is helpful to prevent the spread and use of adulterated herbal materials in time.

Effects of lactoferrin on the production of interferon-λ by the human intestinal epithelial cell line HT-29.

PubMed

Shin, Kouichirou; Oda, Hirotsugu; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

2017-02-01

We examined the in-vitro effects of bovine lactoferrin (LF) on the production of interferon-λ (IFN-λ), an antiviral cytokine important for the defense of enterocytes, using the human intestinal epithelial cell line HT-29. HT-29 cell cultures were treated with LF for 1 h, and the cultures were stimulated with polyinosinic-polycytidylic acid (poly I:C). LF increased the concentration of IFN-λ in the culture supernatant after stimulation in a dose-dependent manner. A similar increase in the concentration of IFN-λ was observed in the supernatant of cells washed between treatment with LF and stimulation with poly I:C. At 6 and 24 h after stimulation with poly I:C (early and late phases, respectively) treated cultures contained significantly higher concentrations of IFN-λ1 in the culture supernatant, and significantly higher IFN-λ1 and IFN-λ2 mRNA levels, than controls. These results suggest that LF activates the innate cellular immunity of the enterocytes to double-stranded RNA and increases the production of IFN-λ.

Seaweed polysaccharides (laminarin and fucoidan) as functional ingredients in pork meat: an evaluation of anti-oxidative potential, thermal stability and bioaccessibility.

PubMed

Moroney, Natasha C; O'Grady, Michael N; Lordan, Sinéad; Stanton, Catherine; Kerry, Joseph P

2015-04-20

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork.

Effect of Noradrenergic Neurotoxin DSP-4 and Maprotiline on Heart Rate Spectral Components in Stressed and Resting Rats.

PubMed

Kur'yanova, E V; Zhukova, Yu D; Teplyi, D L

2017-07-01

The effects of intraperitoneal DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a noradrenergic neurotoxin) and maprotiline (an inhibitor of norepinephrine reuptake in synapses) on spectral components of heart rhythm variability were examined in outbred male and female rats treated with these agents in daily doses of 10 mg/kg for 3 days. At rest, DSP-4 elevated LF and VLF spectral components in male and female rats. Maprotiline elevated LF and VLF components in males at rest, increased HR and reduced all spectral components in resting females. Stress against the background of DSP-4 treatment sharply increased heart rate and reduced the powers of all spectral components (especially LF and VLF components). In maprotiline-treated rats, stress increased the powers of LF and VLF components. Thus, the central noradrenergic system participates in the formation of LF and VLF spectral components of heart rate variability at rest and especially during stressful stimulation, which can determine the phasic character of changes in the heart rate variability observed in stressed organism.

Cooking quality and starch digestibility of gluten free pasta using new bean flour.

PubMed

Giuberti, Gianluca; Gallo, Antonio; Cerioli, Carla; Fortunati, Paola; Masoero, Francesco

2015-05-15

The use of rice/leguminous blend may be nutritionally convenient in gluten free product manufacturing. Gluten free spaghetti was prepared with rice flour and different concentrations of bean flour (included at levels of 0%, 20% and 40%, w/w) derived from a new developed white-seeded low phytic acid and lectin free (ws+lpa+lf) bean cultivar. Protein, ash and dietary fibre contents increased linearly (P<0.05) while total starch decreased quadratically (P<0.05) with the inclusion of ws+lpa+lf bean flour. The colour of spaghetti was influenced (P<0.05) by ws+lpa+lf bean inclusion. With respect to 0% spaghetti, the inclusion of ws+lpa+lf bean increased linearly (P<0.05) the optimal cooking time and the water absorption capacity, without affecting cooking loss and texture properties. The ws+lpa+lf bean inclusion increases quadratically (P<0.05) the resistant starch content, while decreasing quadratically (P<0.05) the in vitro glycemic index. The partial replacement of rice flour with bean flour can favourably be used in gluten free spaghetti formulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adherence to a low-fat vs. low-carbohydrate diet differs by insulin resistance status.

PubMed

McClain, A D; Otten, J J; Hekler, E B; Gardner, C D

2013-01-01

Previous research shows diminished weight loss success in insulin-resistant (IR) women assigned to a low-fat (LF) diet compared to those assigned to a low-carbohydrate (LC) diet. These secondary analyses examined the relationship between insulin-resistance status and dietary adherence to either a LF-diet or LC-diet among 81 free-living, overweight/obese women [age = 41.9 ± 5.7 years; body mass index (BMI) = 32.6 ± 3.6 kg/m(2)]. This study found differential adherence by insulin-resistance status only to a LF-diet, not a LC-diet. IR participants were less likely to adhere and lose weight on a LF-diet compared to insulin-sensitive (IS) participants assigned to the same diet. There were no significant differences between IR and IS participants assigned to LC-diet in relative adherence or weight loss. These results suggest that insulin resistance status may affect dietary adherence to weight loss diets, resulting in higher recidivism and diminished weight loss success of IR participants advised to follow LF-diets for weight loss. © 2012 Blackwell Publishing Ltd.

Low-frequency magnetic fields do not aggravate disease in mouse models of Alzheimer's disease and amyotrophic lateral sclerosis

PubMed Central

Liebl, Martina P.; Windschmitt, Johannes; Besemer, Anna S.; Schäfer, Anne-Kathrin; Reber, Helmut; Behl, Christian; Clement, Albrecht M.

2015-01-01

Low-frequency magnetic fields (LF-MF) generated by power lines represent a potential environmental health risk and are classified as possibly carcinogenic by the World Health Organization. Epidemiological studies indicate that LF-MF might propagate neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). We conducted a comprehensive analysis to determine whether long-term exposure to LF-MF (50 Hz, 1 mT) interferes with disease development in established mouse models for AD and ALS, namely APP23 mice and mice expressing mutant Cu/Zn-superoxide dismutase (SOD1), respectively. Exposure for 16 months did not aggravate learning deficit of APP23 mice. Likewise, disease onset and survival of SOD1G85R or SOD1G93A mice were not altered upon LF-MF exposure for ten or eight months, respectively. These results and an extended biochemical analysis of protein aggregation, glial activation and levels of toxic protein species suggests that LF-MF do not affect cellular processes involved in the pathogenesis of AD or ALS. PMID:25717019

Seaweed Polysaccharides (Laminarin and Fucoidan) as Functional Ingredients in Pork Meat: An Evaluation of Anti-Oxidative Potential, Thermal Stability and Bioaccessibility

PubMed Central

Moroney, Natasha C.; O’Grady, Michael N.; Lordan, Sinéad; Stanton, Catherine; Kerry, Joseph P.

2015-01-01

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork. PMID:25903283

Deadly Lessons: Understanding Lethal School Violence.

ERIC Educational Resources Information Center

Moore, Mark H., Ed.; Petrie, Carol V., Ed.; Braga, Anthony A., Ed.; McLaughlin, Brenda L., Ed.

This collection of papers is the outcome of the National Academies' effort to glean information from six different case studies of student-perpetrated school shootings. Part 1, "Case Studies of Lethal School Violence," includes: "The Copycat Factor: Mental Illness, Guns, and the Shooting Incident at Heritage High School, Rockdale…

Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.

PubMed

Bruni, Natascia; Capucchio, Maria Teresa; Biasibetti, Elena; Pessione, Enrica; Cirrincione, Simona; Giraudo, Leonardo; Corona, Antonio; Dosio, Franco

2016-06-11

Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).

The search for animal models for Lassa fever vaccine development

PubMed Central

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates. PMID:23256740

The search for animal models for Lassa fever vaccine development.

PubMed

Lukashevich, Igor S

2013-01-01

Lassa virus (LASV) is the most prevalent arenavirus in West Africa and is responsible for several hundred thousand infections and thousands of deaths annually. The sizeable disease burden, numerous imported cases of Lassa fever (LF) and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. Currently there is no licensed LF vaccine and research and devlopment is hampered by the high cost of nonhuman primate animal models and by biocontainment requirements (BSL-4). In addition, a successful LF vaccine has to induce a strong cell-mediated cross-protective immunity against different LASV lineages. All of these challenges will be addressed in this review in the context of available and novel animal models recently described for evaluation of LF vaccine candidates.

[Nuclear transfer of goat somatic cells transgenic for human lactoferrin].

PubMed

Li, Lan; Shen, Wei; Pan, Qing-Yu; Min, Ling-Jiang; Sun, Yu-Jiang; Fang, Yong-Wei; Deng, Ji-Xian; Pan, Qing-Jie

2006-12-01

Transgenic animal mammary gland bioreactors are being used to produce recombinant proteins with appropriate post-translational modifications, and nuclear transfer of transgenic somatic cells is a more powerful method to produce mammary gland bioreactor. Here we describe efficient gene transfer and nuclear transfer in goat somatic cells. Gene targeting vector pGBC2LF was constructed by cloning human lactoferrin (LF) gene cDNA into exon 2 of the milk goat beta-casein gene, and the endogenous start condon was replaced by that of human LF gene. Goat fetal fibroblasts were transfected with linearized pGBC2LF and 14 cell lines were positive according to PCR and Southern blot. The transgenic cells were used as donor cells of nuclear transfer, and some of reconstructed embryos could develop to blastocyst in vitro.

Can Lymphatic Filariasis Be Eliminated by 2020?

PubMed

Rebollo, Maria P; Bockarie, Moses J

2017-02-01

Interventions against neglected tropical diseases (NTD), including lymphatic filariasis (LF), scaled up dramatically after the signing of the London Declaration (LD) in 2012. LF is targeted for elimination by 2020, but some countries are considered not on track to meet the 2020 target using the recommended preventive chemotherapy and morbidity management strategies. In this Opinion article we review the prospects for achieving LF elimination by 2020 in the light of the renewed global action against NTDs and the global efforts to achieve the sustainable development goals (SDGs) by 2030. We conclude that LF can be eliminated by 2020 using cross-sectoral and integrated approaches because of the compound effect of the other SDG activities related to poverty reduction and water and sanitation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enrichment of gluten-free cakes with lupin (Lupinus albus L.) or buckwheat (Fagopyrum esculentum M.) flours.

PubMed

Levent, Hacer; Bilgiçli, Nermin

2011-11-01

In the present study, the effect of debittered lupin flour (LF) and whole buckwheat flour (BF) on the nutritional and sensory quality of gluten-free cake was studied. LF (10, 20, 30 and 40%) and BF (5, 10, 15 and 20%) were partially replaced with corn starch and rice flour mixture (1:1 w/w) in the gluten-free cake recipe. LF increased the protein, calcium, iron, manganese, phosphorus and zinc contents of the cakes, while BF caused a significant increase (P < 0.05) especially in potassium and magnesium contents of the gluten-free cakes. According to the overall acceptability rating, it was concluded that gluten-free cake could be produced with satisfactory results by the addition of LF and BF up to 30% and 10%, respectively.

Stress Indices and Flexibility Factors for 90-Degree Piping Elbows with Straight Pipe Extensions.

DTIC Science & Technology

1982-02-01

Laboratory, Oak Ridge, Tennessee (March 1972). 5. The M.W. Kellogg Company , Design of Piping Systems, Second Edition, John Wiley and Sons, Inc., New York (1964...FLEXIBILITY FACTORS FOR 90-DEGREE PIPING ELBOWS WITH STRAIGHT PIPE EXTENSIONS 6. PERFORMING OrG. REPORT NUMBER = 7. AUTHOR(e S . CONTRACT OR GRANT NUMBER(e...UNCLASSIFIED S /N 0102-LF-014-6601 SECURITY CLAUIFICAION OF THII PAGE (Sie. Det Shtee.E) SECURITY CLASSIFICATION OF THIS PACE (When Does Sat* .*) (Block 20

Transcription factor activating protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma. | Office of Cancer Genomics

Cancer.gov

Despite the identification of MYCN amplification as an adverse prognostic marker in neuroblastoma, MYCN inhibitors have yet to be developed. Here, by integrating evidence from a whole-genome shRNA library screen and the computational inference of master regulator proteins, we identify transcription factor activating protein 4 (TFAP4) as a critical effector of MYCN amplification in neuroblastoma, providing a novel synthetic lethal target.

Dual-frequency glow discharges in atmospheric helium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Xiaojiang; Guo, Ying; Magnetic Confinement Fusion Research Center, Ministry of Education of the People's Republic of China, Shanghai 201620

2015-10-15

In this paper, the dual-frequency (DF) glow discharges in atmospheric helium were experimented by electrical and optical measurements in terms of current voltage characteristics and optical emission intensity. It is shown that the waveforms of applied voltages or discharge currents are the results of low frequency (LF) waveforms added to high frequency (HF) waveforms. The HF mainly influences discharge currents, and the LF mainly influences applied voltages. The gas temperatures of DF discharges are mainly affected by HF power rather than LF power.

[Coupling effects of periodic rewatering after drought stress and nitrogen fertilizer on growth and water and nitrogen productivity of Coffea arabica].

PubMed

Hao, Kun; Liu, Xiao Gang; Zhang, Yan; Han, Zhi Hui; Yu, Ning; Yang, Qi Liang; Liu, Yan Wei

2017-12-01

The effects of periodic rewatering after drought stress and nitrogen fertilizer on growth, yield, photosynthetic characteristics of leaves and water and nitrogen productivity of Coffea arabica (Katim P7963) were studied under different nitrogen application levels in 2.5 consecutive years. Irrigation (periodic rewatering after drought stress) and nitrogen were designed as two factors, with four modes of irrigation, namely, full irrigation (I F-F : 100%ET 0 +100%ET 0 , ET 0 was reference crop evapotranspiration), rewatering after light drought stress (I L-F : 80%ET 0 +100%ET 0 ), rewatering after moderate drought stress (I M-F : 60%ET 0 +100%ET 0 ) and rewatering after severe drought stress (I S-F : 40%ET 0 +100%ET 0 ), and three levels of nitrogen, namely, high nitrogen (N H : 750 kg N·hm -2 each time), middle nitrogen (N M : 500 kg N·hm -2 each time), low nitrogen (N L : 250 kg N·hm -2 each time), and nitrogen was equally applied for 4 times. The results showed that irrigation and nitrogen had significant effect on plant height, stem diameter, yield and water and nitrogen productivity of C. arabica, and plant height and stem diameter showed S-curve with the day ordinal number, and leaf photosynthesis decreased significantly under drought stress but most photosynthesis index recovered somewhat after rewatering. Compared with I F-F , I L-F increased dry bean yield by 6.9%, while I M-F and I S-F decreased dry bean yield by 15.2% and 38.5%, respectively; I L-F and I M-F increased water use efficiency by 18.8% and 6.0%, respectively, while I S-F decreased water use efficiency by 12.1%; I L-F increased nitrogen partial productivity by 6.1%, while I M-F and I S-F decreased nitrogen partial productivity by 14.0% and 36.0%, respectively. Compared with N H , N M increased dry bean yield and water use efficiency by 20.9% and 19.3%, while N L decreased dry bean yield and water use efficiency by 42.4% and 41.9%, respectively; N M and N L increased nitrogen partial productivity by 81.4% and 72.9%, respectively. Compared with I F-F N H , I L-F N M increased dry bean yield, water use efficiency and nitrogen partial productivity by 37.6%, 52.9% and 106.4%, respectively. Regression analysis showed that the yield of dry bean was the maximum (2362 kg·hm -2 ) when the irrigation amount was 318 mm and the nitrogen application amount was 583 kg·hm -2 ; the water use efficiency was the maximum (0.78 kg·m -3 ) when the irrigationamount was 295 mm and the nitrogen application amount was 584 kg·hm -2 , that's to say when yield of dry bean and water use efficiency reach the maximum value at the same time, the combination was the closest to I L-F N M . Therefore, the best combination of water and nitrogen model for C. arabica was I L-F N M .

A New Constraint on Reionization from the Evolution of the Lyα Luminosity Function at z ˜ 6-7 Probed by a Deep Census of z = 7.0 Lyα Emitter Candidates to 0.3L *

NASA Astrophysics Data System (ADS)

Ota, Kazuaki; Iye, Masanori; Kashikawa, Nobunari; Konno, Akira; Nakata, Fumiaki; Totani, Tomonori; Kobayashi, Masakazu A. R.; Fudamoto, Yoshinobu; Seko, Akifumi; Toshikawa, Jun; Ichikawa, Akie; Shibuya, Takatoshi; Onoue, Masafusa

2017-07-01

We detect 20 z = 7.0 Lyα emitter (LAE) candidates to L(Lyα) ˜ 2 × 1042 erg s-1 or 0.3 {L}z=7* and in a volume of 6.1 × 105 Mpc3 in the Subaru Deep Field and the Subaru/XMM-Newton Deep Survey field by 82 hr and 37 hr of Subaru Suprime-Cam narrowband NB973 and reddest optical y-band imaging. We compare their Lyα and UV luminosity functions (LFs) and densities and Lyα equivalent widths (EWs) to those of z = 5.7, 6.6, and 7.3 LAEs from previous Suprime-Cam surveys. The Lyα LF (density) rapidly declines by a factor of ×1.5 (1.9) in L(Lyα) at z = 5.7-6.6 (160 Myr), ×1.5 (1.6) at z = 6.6-7.0 (60 Myr) at the faint end, and ×2.0 (3.8) at z = 7.0-7.3 (40 Myr). Also, in addition to the systematic decrease in EW at z = 5.7-6.6 previously found, two-thirds of the z = 7.0 LAEs detected in the UV continuum exhibit lower EWs than the z = 6.6 ones. Moreover, while the UV LF and density do not evolve at z = 5.7-6.6, they modestly decline at z = 6.6-7.0, implying galaxy evolution contributing to the decline of the Lyα LF. Comparison of the z = 7.0 Lyα LF to the one predicted by an LAE evolution model further reveals that galaxy evolution alone cannot explain all of the decline of the Lyα LF. If we attribute the discrepancy to Lyα attenuation by neutral hydrogen, the intergalactic medium transmission of Lyα photons at z = 7.0 would be {T}{Lyα }{IGM}≤slant 0.6{--}0.7. It is lower (higher) than the {T}{Lyα }{IGM} at z = 6.6 (7.3) derived by previous studies, suggesting rapid increase in neutral fraction at z > 6. Based on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan.

Suicide Lethality: A Concept Analysis.

PubMed

DeBastiani, Summer; De Santis, Joseph P

2018-02-01

Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

Effect of Body Composition on Physiological Responses to Cold-Water Immersion and the Recovery of Exercise Performance.

PubMed

Stephens, Jessica M; Halson, Shona L; Miller, Joanna; Slater, Gary J; Chapman, Dale W; Askew, Christopher D

2018-03-01

To explore the influence of body composition on thermal responses to cold-water immersion (CWI) and the recovery of exercise performance. Male subjects were stratified into 2 groups: low fat (LF; n = 10) or high fat (HF; n = 10). Subjects completed a high-intensity interval test (HIIT) on a cycle ergometer followed by a 15-min recovery intervention (control [CON] or CWI). Core temperature (T c ), skin temperature, and heart rate were recorded continuously. Performance was assessed at baseline, immediately post-HIIT, and 40 min postrecovery using a 4-min cycling time trial (TT), countermovement jump (CMJ), and isometric midthigh pull (IMTP). Perceptual measures (thermal sensation [TS], total quality of recovery [TQR], soreness, and fatigue) were also assessed. T c and TS were significantly lower in LF than in HF from 10 min (T c, LF 36.5°C ± 0.5°C, HF 37.2°C ± 0.6°C; TS, LF 2.3 ± 0.5 arbitrary units [a.u.], HF 3.0 ± 0.7 a.u.) to 40 min (T c , LF 36.1°C ± 0.6°C, HF 36.8°C ±0.7°C; TS, LF 2.3 ± 0.6 a.u., HF 3.2 ± 0.7 a.u.) after CWI (P < .05). Recovery of TT performance was significantly enhanced after CWI in HF (10.3 ± 6.1%) compared with LF (3.1 ± 5.6%, P = .01); however, no differences were observed between HF (6.9% ±5.7%) and LF (5.4% ± 5.2%) with CON. No significant differences were observed between groups for CMJ, IMTP, TQR, soreness, or fatigue in either condition. Body composition influences the magnitude of T c change during and after CWI. In addition, CWI enhanced performance recovery in the HF group only. Therefore, body composition should be considered when planning CWI protocols to avoid overcooling and maximize performance recovery.

α-Adrenergic effects on low-frequency oscillations in blood pressure and R-R intervals during sympathetic activation.

PubMed

Kiviniemi, Antti M; Frances, Maria F; Tiinanen, Suvi; Craen, Rosemary; Rachinsky, Maxim; Petrella, Robert J; Seppänen, Tapio; Huikuri, Heikki V; Tulppo, Mikko P; Shoemaker, J Kevin

2011-08-01

The present study was designed to address the contribution of α-adrenergic modulation to the genesis of low-frequency (LF; 0.04-0.15 Hz) oscillations in R-R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; -40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α-adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low-frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low-frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg(2), P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms(2), P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high-frequency oscillations (0.15-0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP-induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α-adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α-adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.

Comparison of 2 weekly-equalized volume resistance-training routines using different frequencies on body composition and performance in trained males.

PubMed

Yue, Fu Leon; Karsten, Bettina; Larumbe-Zabala, Eneko; Seijo, Marcos; Naclerio, Fernando

2018-05-01

The present study compared the effects of 2 weekly-equalized volume and relative load interventions on body composition, strength, and power. Based on individual baseline maximal strength values, 18 recreationally trained men were pair-matched and consequently randomly assigned to one of the following experimental groups: a low volume per session with a high frequency (LV-HF, n = 9) group who trained for 4 days (Mondays, Tuesdays, Thursdays, and Fridays) or a high volume per session and low frequency (HV-LF, n = 9) group who trained for 2 days (Mondays and Thursdays). Both groups performed 2 different routines over 6 weeks. Participants were tested pre- and post- intervention for maximal strength, upper body power, fat-free mass, limb circumferences, and muscle thickness. Compared with baseline values, both groups increased their fat-free mass (HV-LF: +1.19 ± 1.94; LV-HF: +1.36 ± 1.06 kg, p < 0.05) and vastus medialis thickness (HV-LF: +2.18 ± 1.88, p < 0.01; LV-HF: +1.82 ± 2.43 mm, p < 0.05), but only the HV-LF group enhanced arm circumference (1.08 ± 1.47 cm, p < 0.05) and elbow flexors thickness (2.21 ± 2.81 mm, P < 0.01) values and decreased their fat mass (-2.41 ± 1.10, P < 0.01). Both groups improved (p < 0.01) the maximal loads lifted in the bench press (LV-HF: +0.14 ± 0.01; HV-LF: +0.14 ± 0.01 kg·body mass -1 ) and the squat (LV-HF: +0.14 ± 0.06; HV-LF: 0.17 ± 0.01 kg·body mass -1 ) exercises as well as in upper body power (LV-HF: +0.22 ± 0.25; HV-LF: +0.27 ± 0.22 W·body mass -1 ) Although both training strategies improved performance and lower body muscle mass, only the HV-LF protocol increased upper body hypertrophy and improved body composition.

Determinants of the lethality of climate-related disasters in the Caribbean Community (CARICOM): a cross-country analysis

PubMed Central

Andrewin, Aisha N.; Rodriguez-Llanes, Jose M.; Guha-Sapir, Debarati

2015-01-01

Floods and storms are climate-related hazards posing high mortality risk to Caribbean Community (CARICOM) nations. However risk factors for their lethality remain untested. We conducted an ecological study investigating risk factors for flood and storm lethality in CARICOM nations for the period 1980–2012. Lethality - deaths versus no deaths per disaster event- was the outcome. We examined biophysical and social vulnerability proxies and a decadal effect as predictors. We developed our regression model via multivariate analysis using a generalized logistic regression model with quasi-binomial distribution; removal of multi-collinear variables and backward elimination. Robustness was checked through subset analysis. We found significant positive associations between lethality, percentage of total land dedicated to agriculture (odds ratio [OR] 1.032; 95% CI: 1.013–1.053) and percentage urban population (OR 1.029, 95% CI 1.003–1.057). Deaths were more likely in the 2000–2012 period versus 1980–1989 (OR 3.708, 95% CI 1.615–8.737). Robustness checks revealed similar coefficients and directions of association. Population health in CARICOM nations is being increasingly impacted by climate-related disasters connected to increasing urbanization and land use patterns. Our findings support the evidence base for setting sustainable development goals (SDG). PMID:26153115

Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway.

PubMed

Leow, San Min; Chua, Shu Xian Serene; Venkatachalam, Gireedhar; Shen, Liang; Luo, Le; Clement, Marie-Veronique

2017-03-07

Here we provide evidence to link sub-lethal oxidative stress to lysosome biogenesis. Exposure of cells to sub-lethal concentrations of exogenously added hydrogen peroxide resulted in cytosol to nuclear translocation of the Transcription Factor EB (TFEB), the master controller of lysosome biogenesis and function. Nuclear translocation of TFEB was dependent upon the activation of a cathepsin-caspase 3 signaling pathway, downstream of lysosomal membrane permeabilization and accompanied by a significant increase in lysosome numbers as well as induction of TFEB-dependent lysosome-associated genes expression such as Ctsl, Lamp2 and its spliced variant Lamp2a, Neu1and Ctsb and Sqstm1 and Atg9b. The effects of sub-lethal oxidative stress on lysosomal gene expression and biogenesis were rescued upon gene silencing of caspase 3 and TFEB. Notably, caspase 3 activation was not associated with phenotypic hallmarks of apoptosis, evidenced by the absence of caspase 3 substrate cleavage, such as PARP, Lamin A/C or gelsolin. Taken together, these data demonstrate for the first time an unexpected and non-canonical role of a cathepsin-caspase 3 axis in the nuclear translocation of TFEB leading to lysosome biogenesis under conditions of sub-lethal oxidative stress.

Variation in the coding and 3' untranslated regions of the porcine prolactin receptor short form modifies protein expression and function.

PubMed

Trott, Josephine F; Freking, Bradley A; Hovey, Russell C

2014-02-01

The actions of prolactin (PRL) are mediated by both long (LF) and short isoforms (SF) of the PRL receptor (PRLR). Here, we report on a genetic and functional analysis of the porcine PRLR (pPRLR) SF. Three single nucleotide polymorphisms (SNPs) within exon 11 of the pPRLR-SF give rise to four amino acid haplotypes of the intracellular domain. We identified the dimorphic insertion of a short interspersed repetitive DNA element (PRE-1) along with 32 SNPs and four other insertion/deletion sites within the 3' untranslated region (UTR) of pPRLR-SF. The PRE-1 element reduced protein translation in vitro by 75%, whereas the combination of 10 SNPs and one insertion/deletion decreased translation by 50%. Full-length cDNAs for all four haplotypes of pPRLR-SF were cloned behind the elongation factor 1-alpha promoter and functionally analyzed in vitro. None of the haplotypes could initiate transcription from the ß-casein promoter, whereas all four were dominant negatives against PRL-activation of the pPRLR-LF. Two of the haplotypes completely inhibited pPRLR-LF activity at a four-fold excess, whereas the others required a six-fold excess to impart the same effect. The ligand binding affinities of the pPRLR-SF haplotypes did not differ. Expression of the pPRLR-SF increased linearly during gestation in the endometrium and was hormonally regulated in a tissue-specific manner in the mammary glands and uterus. In conclusion, we identified a PRE-1 and other SNPs in the pPRLR-SF 3' UTR that reduce protein expression and four haplotypes of the pPRLR-SF that suppress pPRLR-LF signaling and may differentially impact the phenotypic effects of PRL in vivo. © 2013 Stichting International Foundation for Animal Genetics.