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

RESUMO

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.


Assuntos
Reação de Fase Aguda/veterinária , Bico/fisiologia , Carotenoides/fisiologia , Febre/veterinária , Comportamento de Doença , Aves Canoras/fisiologia , Reação de Fase Aguda/etiologia , Reação de Fase Aguda/metabolismo , Animais , Dieta , Suplementos Nutricionais/análise , Feminino , Febre/etiologia , Febre/metabolismo , Tentilhões/fisiologia , Masculino , Pigmentação
2.
J Infect Dis ; 209(9): 1469-78, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24286983

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mucoproteínas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Sequência de Aminoácidos , Animais , Antibacterianos/farmacocinética , Bacteriemia/microbiologia , Biofilmes , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Modelos Moleculares , Dados de Sequência Molecular , Mucoproteínas/química , Prófagos/enzimologia , Prófagos/genética , Infecções Estafilocócicas/microbiologia , Proteínas Virais/farmacologia
3.
Toxicol Appl Pharmacol ; 259(1): 38-44, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22178736

RESUMO

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.


Assuntos
Asma/induzido quimicamente , Asma/patologia , Cromo/toxicidade , Material Particulado/toxicidade , Animais , Asma/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Feminino , Exposição por Inalação/efeitos adversos , Interleucina-13/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Ovalbumina/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
4.
Ther Adv Infect Dis ; 9: 20499361221117974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992495

RESUMO

Background: Patients with substance use disorders (SUDs) and severe bacterial infections requiring prolonged antibiotic therapy represent a significant challenge to providers due to complexity of care coordination required to ensure safe and effective treatment. Our institution developed a patient-centered multidisciplinary discharge planning conference, OPTIONS-DC, to address this challenge. Methods: We conducted a retrospective review to evaluates parameters between patients who received an OPTIONS-DC and those who did not. Results: We identified 73 patients receiving an OPTIONS-DC and 100 who did not. More patients with an OPTIONS-DC were < 40 years of age (76.7% versus 61.0%, OR = 2.3, 95% CI = 1.1-4.7, p = 0.02), had positive HCV antibody testing (58.9% versus 41.0%, OR = 2.1, 95% CI = 1.1-3.8, p = 0.02), injection drug use (93.2% versus 79.0%, OR = 3.6 95% CI = 1.3-10.1, p = 0.01), used methamphetamines (84.9% versus 72.0%, OR = 2.2, 95% CI = 1.0-4.8, p = 0.04), and started inpatient SUD treatment (80.8% versus 63%, OR = 2.5, 95% CI = 1.2-5.0, p = 0.04) compared with those without a conference. The OPTIONS-DC group was more likely to be diagnosed with bacteremia (74.0% versus 57.0%, OR = 2.1, 95% CI = 1.1-4.1, p = 0.02), endocarditis (39.7% versus21.0%, OR = 2.5, 95% CI = 1.3-4.9, p = 0.03), vertebral osteomyelitis (45.2% versus 15.0%, OR = 4.7, 95% CI = 2.3-9.6, p < 0.01), and epidural abscess (35.6% versus 10.0%, OR = 5.0, 95% CI = 2.2-11.2, p < 0.01) and require 4 weeks or more of antibiotic treatment (97.3% versus 51.1%, OR = 34.1, 95% CI = 7.9-146.7, p = 0.01). Patients with an OPTIONS-DC were also more likely to be admitted between 2019 and 2020 than between 2018 and 2019 (OR = 4.1, 95% CI = 2.1-7.9, p < 0.01). Conclusion: Patients with an OPTIONS-DC tended to have more complicated infections and longer courses of antibiotic treatment. While further research on outcomes is needed, patients receiving an OPTIONS-DC were able to successfully complete antibiotic courses across a variety of settings.

6.
Hum Vaccin ; 7(11): 1234-44, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22064562

RESUMO

The human hookworms Necator americanus and Ancylostoma duodenale remain among the most common infections of humans in areas of rural poverty in the developing regions of the world, with an estimated 1 billion people infected with one or more of these parasites. Herein, we review the nearly 100 years of research, development, animal testing, and fieldwork that have led to our current progress in recombinant hookworm vaccines. We begin with the identification of hookworm at the start of the 20th century in Southern US, then discuss the progress in developed countries to eliminate human hookworm infection, and then the industrial development and field use in the 1970s a canine hookworm vaccine(Ancylostoma caninum), and finally our progress to date in the development and clinical testing of an array of recombinant antigens to prevent human hookworm disease from N. americanus infection. Special attention is given to the challenges faced in the development of a vaccine against a blood-feeding nematode, including the epidemiology of infection (high prevalence of infection), pathogenesis (chronic infection that increases with the age of the host), and a robust immune response that fails to confer the protection in the host and a concomitant absence of correlates of protection by a successful vaccine could be developed and tested. Finally, we provide the optimal and acceptable profiles of a human hookworm vaccine, including the proposed indication, target population, and route of administration, as developed by the Human Hookworm Vaccine Initiative, the only group currently working on vaccines targeting this parasite.


Assuntos
Ancylostomatoidea/imunologia , Ancilostomíase/prevenção & controle , Necatoríase/prevenção & controle , Vacinas Sintéticas/imunologia , Ancylostoma/imunologia , Ancylostomatoidea/genética , Ancilostomíase/imunologia , Ancilostomíase/veterinária , Animais , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Doenças do Cão/imunologia , Doenças do Cão/prevenção & controle , Cães , Humanos , Necator americanus/imunologia , Necatoríase/imunologia
7.
Eukaryot Cell ; 8(6): 899-912, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19286988

RESUMO

We describe a novel pair of nested genes, CDA12 and CDA13, from Tetrahymena thermophila. Both are implicated in membrane trafficking associated with cell division and conjugation. Green fluorescent protein localization reveals Cda12p decoration of diverse membrane-bound compartments, including mobile, subcortical tubulovesicular compartments; perinuclear vesicles; and candidates for recycling endosomes. Cda13p decorates intracellular foci located adjacent to cortically aligned mitochondria and their neighboring Golgi networks. The expression of antisense CDA12 RNA in transformants produces defects in cytokinesis, macronuclear segregation, and the processing of pinosomes to downstream compartments. Antisense CDA13 RNA expression produces a conjugation phenotype, resulting in the failure of mating pairs to separate, as well as failures in postconjugation cytokinesis and macronuclear fission. This study offers insight into the membrane trafficking events linking endosome and Golgi network activities, cytokinesis, and karyokinesis and the unique membrane-remodeling events that accompany conjugation in the ciliate T. thermophila. We also highlight an unusual aspect of genome organization in Tetrahymena, namely, the existence of nested, antisense genes.


Assuntos
Membrana Celular/metabolismo , Genes Inseridos , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismo , Animais , Membrana Celular/genética , Citocinese , Dados de Sequência Molecular , Transporte Proteico , Tetrahymena thermophila/citologia
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