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1.
J Exp Biol ; 220(Pt 16): 2957-2964, 2017 08 15.
Article in English | MEDLINE | ID: mdl-28606898

ABSTRACT

Carotenoids are finite resources that animals can allocate to self-maintenance, attractiveness or reproduction. Here we test how carotenoids affect the acute phase response (APR), an intense rapid systemic response characterized by fever, sickness behavior and production of acute phase proteins, which serves to reduce pathogen persistence. We conducted a 2×2 factorial design experiment in captive adult male and female zebra finches (Taeniopygia guttata) to determine the effects of carotenoid supplementation on the intensity of the APR. We measured changes in feeding rate, activity level and body temperature of the birds. We found that, relative to unsupplemented controls, carotenoid-supplemented birds exhibited less severe reductions in feeding and activity, smaller increases in body temperature and lower circulating levels of haptoglobin (an acute phase protein) 24 h after inducing an APR. Among supplemented individuals, those with higher blood carotenoid levels exhibited a lower reduction in activity rate after 24 h. Forty-eight hours after APR induction, birds exhibited a significant decrease in plasma carotenoid levels and a decrease in bill hue, with less reduction in hue in carotenoid-supplemented individuals. These results demonstrate that carotenoids can alleviate several important behavioral and physiological effects of an APR and that bill color can change rapidly following induction of the costly APR immune defense. In particular, immune activation may have caused birds to preferentially draw down carotenoids from the bloodstream, ostensibly for use in health. Rapid bill color changes over a 48-h period support growing evidence that bills may serve as short-term signals of health and condition.


Subject(s)
Acute-Phase Reaction/veterinary , Beak/physiology , Carotenoids/physiology , Fever/veterinary , Illness Behavior , Songbirds/physiology , Acute-Phase Reaction/etiology , Acute-Phase Reaction/metabolism , Animals , Diet , Dietary Supplements/analysis , Female , Fever/etiology , Fever/metabolism , Finches/physiology , Male , Pigmentation
2.
J Infect Dis ; 209(9): 1469-78, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24286983

ABSTRACT

Lysins are bacteriophage-derived enzymes that degrade bacterial peptidoglycans. Lysin CF-301 is being developed to treat Staphylococcus aureus because of its potent, specific, and rapid bacteriolytic effects. It also demonstrates activity on drug-resistant strains, has a low resistance profile, eradicates biofilms, and acts synergistically with antibiotics. CF-301 was bacteriolytic against 250 S. aureus strains tested including 120 methicillin-resistant S. aureus (MRSA) isolates. In time-kill studies with 62 strains, CF-301 reduced S. aureus by 3-log10 within 30 minutes compared to 6-12 hours required by antibiotics. In bacteremia, CF-301 increased survival by reducing blood MRSA 100-fold within 1 hour. Combinations of CF-301 with vancomycin or daptomycin synergized in vitro and increased survival significantly in staphylococcal-induced bacteremia compared to treatment with antibiotics alone (P < .0001). Superiority of CF-301 combinations with antibiotics was confirmed in 26 independent bacteremia studies. Combinations including CF-301 and antibiotics represent an attractive alternative to antibiotic monotherapies currently used to treat S. aureus bacteremia.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Mucoproteins/pharmacology , Staphylococcal Infections/drug therapy , Amino Acid Sequence , Animals , Anti-Bacterial Agents/pharmacokinetics , Bacteremia/microbiology , Biofilms , Drug Synergism , Female , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Models, Molecular , Molecular Sequence Data , Mucoproteins/chemistry , Prophages/enzymology , Prophages/genetics , Staphylococcal Infections/microbiology , Viral Proteins/pharmacology
3.
Toxicol Appl Pharmacol ; 259(1): 38-44, 2012 Feb 15.
Article in English | MEDLINE | ID: mdl-22178736

ABSTRACT

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels.


Subject(s)
Asthma/chemically induced , Asthma/pathology , Chromium/toxicity , Particulate Matter/toxicity , Animals , Asthma/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Female , Inhalation Exposure/adverse effects , Interleukin-13/immunology , Lung/drug effects , Lung/immunology , Lung/pathology , Mice , Mice, Inbred BALB C , Neutrophil Infiltration/drug effects , Neutrophil Infiltration/immunology , Ovalbumin/immunology , Respiratory Mucosa/drug effects , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , Th2 Cells/drug effects , Th2 Cells/immunology
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