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1.
Osteoporos Int ; 31(7): 1189-1191, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32346775

RESUMO

As the world grapples with the crisis of COVID-19, established economies and healthcare systems have been brought to their knees. Tough decisions regarding redirection of resources away from the management of conditions deemed "nonessential" are being made. How can we balance urgent resourcing of our acute crisis while not abandoning the real need of patients with osteoporosis? This article offers a few practical solutions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Alocação de Recursos para a Atenção à Saúde/organização & administração , Osteoporose/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/diagnóstico , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Infecções por Coronavirus/diagnóstico , Denosumab/administração & dosagem , Diagnóstico Diferencial , Difosfonatos/efeitos adversos , Esquema de Medicação , Humanos , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Educação de Pacientes como Assunto , Pneumonia Viral/diagnóstico , Medição de Risco/métodos
2.
Nat Med ; 26(4): 511-518, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32251406

RESUMO

Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease1,2 and nominating testable therapeutic targets3. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability4. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection5, we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.


Assuntos
Comunicação Celular , Infecções por HIV/genética , Infecções por HIV/imunologia , Imunidade Celular/fisiologia , Análise de Célula Única/métodos , Doença Aguda , Reação de Fase Aguda/genética , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/patologia , Adolescente , Adulto , Comunicação Celular/genética , Comunicação Celular/imunologia , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/imunologia , Infecções por HIV/patologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Estudos Longitudinais , Análise de Sequência de RNA/métodos , Integração de Sistemas , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Carga Viral/genética , Carga Viral/imunologia , Adulto Jovem
3.
Subcell Biochem ; 94: 421-436, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189310

RESUMO

As normal constituents of blood serum, the Serum Amyloid A (SAA) proteins are small (104 amino acids in humans) and remarkably well-conserved in mammalian evolution. They are synthesized prominently, but not exclusively, in the liver. Fragments of SAA can associate into insoluble fibrils (called "amyloid") characteristic of "secondary" amyloid disease in which they can interrupt normal physiology and lead to organ failure. SAA proteins comprise a family of molecules, two members of which (SAA1 and SAA2) are (along with C-reactive protein, CRP) the most prominent members of the acute phase response (APR) during which their serum levels rise dramatically after trauma, infection and other stimuli. Biologic function (s) of SAA are unresolved but features are consistent with a prominent role in primordial host defense (including the APR ). SAA proteins are lipophilic and contribute to high density lipoproteins (HDL) and cholesterol transport. SAA proteins interact with specific receptors and have been implicated in tissue remodeling through metalloproteinases, local tissue changes in atherosclerosis, cancer metastasis, lung inflammation, maternal-fetal health and intestinal physiology. Molecular details of some of these are emerging.


Assuntos
Proteína Amiloide A Sérica , Reação de Fase Aguda , Amiloide/química , Amiloide/metabolismo , Animais , Colesterol/metabolismo , Doença , Humanos , Lipoproteínas HDL/metabolismo , Fígado/metabolismo , Proteína Amiloide A Sérica/química , Proteína Amiloide A Sérica/metabolismo
4.
PLoS One ; 15(2): e0229009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045459

RESUMO

Broiler chickens experience an acute-phase response (APR) through vaccination, which reflects the innate immunity and stress related to immunization. It is also considered that APR can modulate adaptive immunity and response to infection. As biomarkers for APR, assessing the acute-phase proteins (APPs) function and their levels in response to immunization is of great value for vaccine design, development and administration. In this study, the heterophils/lymphocyte (H/L) ratio and the level of APPs was evaluated in broilers with three different Newcastle disease (ND) vaccination regimens. Inactivated ND vaccine (IND) was administered by the intramuscular route. Live attenuated strains, Lasota and Vitapest, was administered by ocular routes. H/L ratio, serum amyloid A (SAA) and alpha-1 acid glycoprotein (AGP) were measured before and after two rounds of vaccination on days 10 and 21. In a comparison between the three vaccines, H/L ratio in IND group significantly increased to 3 fold (1.48 ± 0.41) after the first vaccination while the Lasota and Vitapest showed a milder response. The concentration of SAA increased after 24h by 1.8-fold in IND group (0.116 ± 0.015 mg/L) and 2-fold in Lasota group (0.14 ± 0.002 mg/L). Significant changes were found in Vitapest group after 48h post vaccination (0.113 ± 0.016 mg/L). Elevation pattern of AGP, 24 hours after first vaccination in IND (3.5-fold) and Vitapest (2.5-fold) was different from Lasota in which the peak was reached after 48 hours (2.9-fold). Except for IND group, no significant changes in SAA and AGP concentrations were detected after the second vaccination. A significant positive correlation between SAA values at day 22 and HI titers at day 28 (r = 0.998, P≤0. 0.005) was found. According to these results, different types of ND vaccines can cause different patterns of acute phase responses. Assessment of stress and level of acute-phase proteins can be used for prediction of immune response outcomes in vaccine design and development.


Assuntos
Reação de Fase Aguda/imunologia , Proteínas Aviárias/imunologia , Proteínas Sanguíneas/imunologia , Galinhas/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Vacinação , Vacinas Virais/imunologia , Animais , Doença de Newcastle/imunologia , Fatores de Tempo
5.
Environ Toxicol Pharmacol ; 73: 103266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707308

RESUMO

The toxicological potential of halloysite nanotubes (HNTs) and variants after functional alterations to surface area are not clear. We assessed the toxicological response to HNTs (NaturalNano (NN)) before and after surface etching (NN-etched). Potential cytotoxicity of the two HNTs was screened in vitro in MutaTMMouse lung epithelial cells. Lung inflammation, acute phase response and genotoxicity were assessed 1, 3, and 28 days after a single intratracheal instillation of adult female C57BL/6 J BomTac mice. The doses were 6, 18 or 54 µg of HNTs, compared to vehicle controls and the Carbon black NP (Printex 90) of 162 µg/mouse. The cellular composition of bronchoalveolar lavage (BAL) fluid was determined as a measure of lung inflammation. The pulmonary and hepatic acute phase responses were assessed by Serumamyloida mRNA levels in lung and liver tissue by real-time quantitative PCR. Pulmonary and systemic genotoxicity were analyzed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The etched HNT (NN-etched) had 4-5 times larger BET surface area than the unmodified HNT (NN). Instillation of NN-etched at the highest dose induced influx of neutrophils into the lungs at all time points and increased Saa3 mRNA levels in lung tissue on day 1 and 3 after exposure. No genotoxicity was observed at any time point. In conclusion, functionalization by etching increased BET surface area of the studied NN and enhanced pulmonary inflammatory toxicity in mice.


Assuntos
Reação de Fase Aguda , Argila , Pulmão/efeitos dos fármacos , Nanotubos/toxicidade , Animais , Líquido da Lavagem Broncoalveolar , Ensaio Cometa , Camundongos , Camundongos Endogâmicos C57BL , Nanotubos/química , Pneumonia
6.
Res Vet Sci ; 127: 57-64, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31678454

RESUMO

The objective of this study was to evaluate the effects of in-feed clinoptilolite (CPL) on serum metabolic and antioxidative biomarkers, acute phase proteins and reproductive performance in cows during pregnancy and lactation. A total of 78 Holstein-Friesian cows were randomly assigned into two groups: the treatment group, cows fed CPL (n = 38) which received 50 g of powdered CPL twice a day from day 180 before parturition to day 60 postpartum; and the control group (n = 40). Blood samples were taken on days 180, 90, 60, 30 and 10 before parturition, on day of calving and on days 5, 12, 19, 26, 33, 40 and 60 postpartum, and were analysed for metabolic biomarkers: glucose, triglycerides, total cholesterol, high density lipoprotein cholesterol, non-esterified fatty acids, beta-hydroxybutyrate (BHB), antioxidative biomarkers and acute phase proteins: paraoxonase-1 (PON1), apolipoprotein A-I, haptoglobin (Hp) and serum amyloid A (SAA). CPL supplementation increased concentration of glucose and significantly decreased (P < .05) level of BHB during puerperium. The SAA concentration in CPL-fed cows was significantly decreased (P < .05) on days 33, 40 and 60 postpartum as well as Hp concentration on days 0 and 12 postpartum. The results of this study suggest that the CPL-fed cows may have improved metabolic status due to the tendency of greater glucose levels and decreased BHB values during early lactation. In addition, acute phase response was lower (P < .05) in CPL-fed cows. Such an outcome might be attributed to the effect of dietary CPL on intensity and severity of the negative energy balance and inflammatory response in dairy cows.


Assuntos
Reação de Fase Aguda/veterinária , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Doenças dos Bovinos/tratamento farmacológico , Zeolitas/metabolismo , Reação de Fase Aguda/tratamento farmacológico , Reação de Fase Aguda/metabolismo , Ração Animal/análise , Animais , Bovinos , Doenças dos Bovinos/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Lactação/fisiologia , Gravidez , Distribuição Aleatória , Soro/metabolismo , Zeolitas/administração & dosagem
7.
Int J Chron Obstruct Pulmon Dis ; 14: 1323-1332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417249

RESUMO

Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.


Assuntos
Reação de Fase Aguda , Pulmão , Linfócitos/imunologia , Artéria Pulmonar , Doença Pulmonar Obstrutiva Crônica , Proteína Amiloide A Sérica/análise , Proteínas da Fase Aguda/análise , Proteínas da Fase Aguda/imunologia , Reação de Fase Aguda/sangue , Reação de Fase Aguda/imunologia , Correlação de Dados , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/imunologia , Artéria Pulmonar/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/patologia , Espirometria/métodos
8.
Nanotoxicology ; 13(9): 1275-1292, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31441356

RESUMO

Inhalation of nanosized zinc oxide (ZnO) induces metal fume fever and systemic acute phase response in humans. Acute phase response activation is a cardiovascular risk factor; we investigated whether pulmonary exposure of mice can be used to assess ZnO-induced acute phase response as well as inflammation and genotoxicity. Uncoated (NM-110) and triethoxycaprylylsilane-coated (NM-111) ZnO nanoparticles were intratracheally instilled once at 0.2, 0.7 or 2 µg/mouse (11, 33 and 100 µg/kg body weight). Serum amyloid A3 mRNA level in lung tissue, bronchoalveolar lavage (BAL) fluid cellularity, and levels of DNA strand breaks in BAL fluid cells, lung and liver tissue were assessed 1, 3 and 28 days post-exposure. Global transcription patterns were assessed in lung tissue using microarrays. The acute-phase response serum amyloid A3 mRNA levels were increased on day 1; for uncoated ZnO nanoparticles at the highest dose and for coated ZnO nanoparticles at medium and highest dose. Neutrophils were increased in BAL fluid only after exposure to coated ZnO nanoparticles. Genotoxicity was observed only in single dose groups, with no dose-response relationship. Most changes in global transcriptional response were observed after exposure to uncoated ZnO nanoparticles and involved cell cycle G2 to M phase DNA damage checkpoint regulation. Although, uncoated and coated ZnO nanoparticles qualitatively exerted similar effects, observed differences are likely explained by differences in solubility kinetics. The finding of serum amyloid A3 induction at low exposure suggests that mouse models can be used to assess the nanoparticle-mediated induction of acute phase responses in humans.


Assuntos
Reação de Fase Aguda , Inflamação/induzido quimicamente , Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Óxido de Zinco/toxicidade , Administração por Inalação , Animais , Líquido da Lavagem Broncoalveolar/citologia , Dano ao DNA , Relação Dose-Resposta a Droga , Humanos , Inflamação/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos , RNA Mensageiro/genética , Traqueia/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-31450831

RESUMO

Although patients under supportive periodontal therapy (SPT) have a stable periodontal condition, the acute symptom of chronic periodontal disease occasionally occurs without a clear reason. Therefore, in the present study, to obtain a better understanding of this relationship in patients undergoing SPT, we hypothesized that the acute symptom of chronic periodontal disease might be affected by climate factors. We conducted a questionnaire study and carried out oral examinations on patients undergoing SPT who had been diagnosed as having the acute symptom of chronic periodontal disease. We collected climate data from the local climate office in Okayama city, Japan. We predicted parameters that affect the acute symptom of chronic periodontal disease with unidentified cause and divided patients into high and low groups in terms of climate predictors. Then we defined the cut-off values of parameters showing significant differences in the incidence of the acute symptom of chronic periodontal disease. The incidence of the acute symptom of chronic periodontal disease with unidentified cause was significantly different when the cases were classified according to the maximum hourly decrease in barometric pressure (1.5 and 1.9 hPa) (p = 0.04 and p = 0.03, respectively). This suggests that climate variables could be predictors of the acute symptom of chronic periodontal disease. Therefore, gaining a better understanding of these factors could help periodontal patients undergoing SPT prepare to avoid the acute symptom of chronic periodontal disease.


Assuntos
Periodontite Crônica/etiologia , Assistência Odontológica/estatística & dados numéricos , Reação de Fase Aguda , Idoso , Periodontite Crônica/epidemiologia , Periodontite Crônica/terapia , Clima , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
10.
Acta Vet Scand ; 61(1): 36, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345246

RESUMO

Bovine coronavirus (BCoV) is associated with severe diarrhea in calves, winter dysentery in adult cattle, and respiratory diseases in cattle of all ages. This study aimed to investigate the relationship between white blood cell counts and haptoglobin (Hp) and serum amyloid A (SAA) levels in post-weaned calves with diarrhea caused by BCoV and those that recovered from diarrhea. Blood and fecal samples were collected twice from the same animals; 17 post-weaned calves with diarrhea (first) and 15 post-weaned calves that recovered from diarrhea (second). Real-time polymerase chain reaction revealed that all 17 fecal samples from post-weaned calves with diarrhea and one out of 15 from diarrhea-recovered calves were positive for BCoV and negative for Cryptosporidium spp., Escherichia coli K99, Salmonella spp., bovine rotavirus, and bovine viral diarrhea virus. No Eimeria oocysts were detected using the flotation method. In comparison with post-weaned calves with diarrhea, in diarrhea-recovered calves, the lymphocyte count was significantly higher (P = 0.018), and the monocyte count was significantly lower (P = 0.001); however, the number of monocytes was still high. Post-weaned calves with diarrhea had a significantly higher Hp concentration (P < 0.001) compared with diarrhea-recovered calves. The results indicated that increased Hp concentration and monocytosis but not SAA may be associated with diarrhea caused by BCoV. The present study suggests that the monitoring of Hp concentration and monocyte count is useful in the diagnosis of post-weaned calves with diarrhea caused by BCoV in this field.


Assuntos
Reação de Fase Aguda/veterinária , Doenças dos Bovinos/imunologia , Infecções por Coronavirus/veterinária , Diarreia/veterinária , Reação de Fase Aguda/sangue , Reação de Fase Aguda/imunologia , Animais , Bovinos , Doenças dos Bovinos/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Coronavirus Bovino , Diarreia/sangue , Diarreia/etiologia , Diarreia/imunologia , Fezes/virologia , Feminino , Haptoglobinas/análise , Contagem de Linfócitos , Proteína Amiloide A Sérica/análise , Desmame
11.
Res Vet Sci ; 125: 290-297, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31349186

RESUMO

Endotoxemia treatment options are still of interest due to high mortality and choline treatment is one of them because of its role in the cholinergic anti-inflammatory pathway. This study investigated serum choline and butyrylcholinesterase (BChE) responses, and their correlations with inflammatory, oxidative stress and tissue damage biomarkers, including paraoxanase-1 (PON1), and clinical signs in calves with endotoxemia and the effect of choline treatment in these responses. Healthy calves (n = 20) were divided equally into 4 groups: Control (0.9% NaCl, iv), Choline (C; 1 mg/kg/iv,once), Lipopolysaccharide (LPS; 2 µg/kg/iv,once) and LPS + C. Clinical and laboratory examinations were performed before and 0.5-48 h (hrs) after treatments. Following LPS administration, serum choline level increased at 0.5-24 h (P < .01), whereas serum BChE and PON1 level decreased at 48 h (P < .01) compared to their baselines. In LPS + C group, the increase in serum choline level was significantly higher (P < .01) than that of C and LPS groups. LPS did not decrease serum BChE levels significantly in calves treated with choline. Serum choline and BChE results correlated negatively with white blood cell count and positively (P < .001) with PON1 levels, oxidative stress index, inflammation and hepato-muscular injury markers. In conclusion serum choline and BChE may have a role in the pathophysiology of endotoxemia in calves. High serum choline concentration is associated with an improvement in response to LPS administration in calves treated with choline, probably by preventing the imbalances between oxidative stress and anti-oxidant capacity, preventing the serum BChE and PON1 decreases, and inhibition/attenuation of acute phase reaction and hepato-muscular injury in calves with endotoxemia.


Assuntos
Butirilcolinesterase/sangue , Doenças dos Bovinos/induzido quimicamente , Colina/sangue , Endotoxemia/veterinária , Lipopolissacarídeos/toxicidade , Reação de Fase Aguda/tratamento farmacológico , Administração Intravenosa , Animais , Biomarcadores/sangue , Butirilcolinesterase/metabolismo , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/tratamento farmacológico , Endotoxemia/tratamento farmacológico , Endotoxemia/fisiopatologia , Inflamação/tratamento farmacológico , Contagem de Leucócitos , Lipopolissacarídeos/administração & dosagem , Masculino , Estresse Oxidativo , Distribuição Aleatória
12.
Neuron ; 103(5): 820-835.e7, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31301936

RESUMO

The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer's disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenuated amyloid beta (Aß) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout. Knocking out TREM2 in 5xFAD mice exacerbated Aß pathology and neurodegeneration but reduced Iba1+ cell numbers, all of which could not be rescued by additional CD33 knockout. RNA-seq profiling of microglia revealed that genes related to phagocytosis and signaling (IL-6, IL-8, acute phase response) are upregulated in 5xFAD;CD33-/- and downregulated in 5xFAD;TREM2-/- mice. Differential gene expression in 5xFAD;CD33-/- microglia depended on the presence of TREM2, suggesting TREM2 acts downstream of CD33. Crosstalk between CD33 and TREM2 includes regulation of the IL-1ß/IL-1RN axis and a gene set in the "receptor activity chemokine" cluster. Our results should facilitate AD therapeutics targeting these receptors.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Cognição , Glicoproteínas de Membrana/genética , Microglia/metabolismo , Placa Amiloide/patologia , Receptores Imunológicos/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Reação de Fase Aguda/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Camundongos , Camundongos Knockout , Microglia/patologia , Fagocitose/genética
13.
Infect Immun ; 87(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31160364

RESUMO

Pneumonia and sepsis are distinct but integrally linked public health concerns. The hepatic acute-phase response (APR), which is largely dependent on transcription factors NF-κB RelA and STAT3, is a hallmark of these pathologies and other injurious conditions. Inactivation of the APR can promote liver injury, a frequently observed organ dysfunction during sepsis. However, whether or how the acute-phase changes promote liver tissue resilience during infections is unclear. To determine the hepatoprotective role of the hepatic APR, we utilized mice bearing hepatocyte-specific deletions of either RelA or STAT3. Mice were challenged intratracheally (i.t.), intravenously (i.v.), or intraperitoneally (i.p.) with Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, lipopolysaccharide (LPS), or alpha-galactosylceramide (αGalCer) to induce pneumonia, sepsis, or NKT cell activation. Liver injury was observed in RelA-null (hepRelAΔ/Δ) mice but not STAT3-null (hepSTAT3Δ/Δ) mice during pneumonia. The absence of RelA resulted in hepatotoxicity across several models of pneumonia, sepsis, and NKT cell activation. Injury was associated with increased levels of activated caspase-3 and -8 and substantial alteration of the hepatic transcriptome. Hepatotoxicity in the absence of RelA could be reversed by neutralization of tumor necrosis factor alpha (TNF-α). These results indicate the requirement of RelA-dependent inducible hepatoprotection during pneumonia and sepsis. Further, the results demonstrate that RelA-dependent gene programs are critical for maintaining liver homeostasis against TNF-α-driven immunotoxicity.


Assuntos
Fígado/patologia , Pneumonia/patologia , Sepse/patologia , Fator de Transcrição RelA/fisiologia , Reação de Fase Aguda , Animais , Apoptose , Quimiocina CCL2/fisiologia , Macrófagos do Fígado/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/imunologia , Fator de Transcrição STAT3/fisiologia , Fator de Necrose Tumoral alfa/fisiologia
14.
J Vet Intern Med ; 33(4): 1686-1694, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31175698

RESUMO

BACKGROUND: Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. HYPOTHESIS: Dogs with B. canis-induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. ANIMALS: Twenty-nine client-owned dogs with acute B. canis infection and 10 clinically healthy control dogs. METHODS: Observational cross-sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA-1 (radioimmunoassay) and SAA was determined. RESULTS: Dogs with B. canis infection had a marked APR (median SAA, 168.3 µg/mL; range, 98.1-716.2 µg/mL) compared with controls (3.2 µg/mL, 2.0-4.2 µg/mL) (P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89-7.64 mmol/L versus 6.15 mmol/L, 4.2-7.4 mmol/L) (P = .02), phospholipid (4.64 mmol/L, 2.6-6.6 mmol/L versus 5.72 mmol/L, 4.68-7.0 mmol/L) (P = .02), and α-lipoproteins (77.5%, 27.7%-93.5% versus 89.2%, 75.1%-93.5%) (P = .04), and higher ApoA-1 (1.36 U, 0.8-2.56 U versus 0.95 U, 0.73-1.54 U) concentrations (P = .02). Serum amyloid A correlated with high-density lipoproteins (HDLs) diameter (rho = .43; P = .03) and ApoA-1 (rho = .63, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Major changes associated with B. canis-induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA-1 and SAA concentration increase is a unique still unexplained pathophysiological finding.


Assuntos
Reação de Fase Aguda/veterinária , Babesiose/sangue , Doenças do Cão/parasitologia , Reação de Fase Aguda/sangue , Reação de Fase Aguda/parasitologia , Animais , Apoproteínas/sangue , Babesia , Babesiose/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Doenças do Cão/sangue , Doenças do Cão/metabolismo , Cães , Feminino , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Proteína Amiloide A Sérica/análise
15.
J Fish Dis ; 42(7): 975-984, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31066066

RESUMO

A previous proteomic study examining the plasma acute-phase response of rainbow trout to sterile inflammation highlighted an unidentified 9.5-kDa spot using 2D-PAGE, which was dramatically increased. The 15 amino acid sequence obtained from this protein spot allowed rapid amplification of cDNA ends PCR to generate a 443-bp nucleotide sequence that was 98.6% similar to type-4 ice-structuring protein LS-12 from Atlantic salmon Salmo salar Linnaeus. Quantitative reverse translation PCR and an ELISA were used to measure gene expression and plasma concentrations of LS-12 following experimental intraperitoneal injection of rainbow trout with either 106 or 108 colony-forming units (CFU) of Flavobacterium psychrophilum. There was no significant change in the plasma concentration of LS-12 up to 15 days post-infection in any group. Hepatic LS-12 gene expression was significantly reduced at 3 and 6 days (p < 0.001) post-infection in fish injected with 108 CFU of F. psychrophilum relative to control fish, while branchial or head kidney expression was unchanged. Infected fish had significantly increased hepatic gene expression of serum amyloid A, confirming an acute-phase response. Under the conditions used, LS-12 is not a positive acute-phase protein in rainbow trout.


Assuntos
Reação de Fase Aguda/veterinária , Doenças dos Peixes/microbiologia , Proteínas de Peixes/genética , Infecções por Flavobacteriaceae/veterinária , Oncorhynchus mykiss/microbiologia , Reação de Fase Aguda/microbiologia , Animais , Proteínas de Peixes/sangue , Infecções por Flavobacteriaceae/microbiologia , Flavobacterium/patogenicidade , Reação em Cadeia da Polimerase , Proteômica
16.
Immunopharmacol Immunotoxicol ; 41(1): 150-162, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31038378

RESUMO

Objective: Recently, many researches with different viewpoints have focused on application of immunotherapy agents in treatment of spinal cord injury (SCI) according to neuroprotective results in some neurodegenerative disease. Glatiramer acetate (GA) is the most commonly used drug for Multiple sclerosis (MS) patients that exerts an immunomodulatory effect against Myelin basic protein (MBP) antigen. Materials and methods: High-dose (2mg/kg) treatment of GA for 28 consecutive days after SCI was compared with its low-dose (0.5 mg/kg) treatment, SCI control and Sham control rat groups. Results: High-dose GA group had significantly worsened outcome in standard functional recovery evaluation test (BBB) 12 weeks after SCI compared to SCI control and low-dose GA groups, which was confirmed by augmented spinal cavity volume and reduced ventral horn motor neurons in high-dose GA group; however, there was no significant difference between low-dose GA and control SCI group. In addition, proliferation test performed on lymphocytes from spleen and lymph nodes one week after SCI showed that high-dose GA injection has more significant effect on Division Index (DI) in response to MBP stimulation compared to low-dose GA and control SCI groups, which was associated with significant increase in IFN-γ, IL-4, and IL-17A secretion. Conclusion: Along with confirmation of deleterious aspects of autoimmunity resulting from autoreactive lymphocytes against myelin antigens in SCI, this study has shown that high-dose immunotherapy using GA, especially in acute phase after SCI, overwhelms any neuroprotective effect of adoptive immune system.


Assuntos
Reação de Fase Aguda/tratamento farmacológico , Acetato de Glatiramer/administração & dosagem , Imunoterapia/métodos , Proteína Básica da Mielina/imunologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Reação de Fase Aguda/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Acetato de Glatiramer/uso terapêutico , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
18.
Adv Clin Chem ; 90: 25-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31122611

RESUMO

Acute-phase reactant serum amyloid A (A-SAA) plays an important role in acute and chronic inflammation and is used in clinical laboratories as an indicator of inflammation. Although both A-SAA and C-reactive protein (CRP) are acute-phase proteins, the detection of A-SAA is more conclusive than the detection of CRP in patients with viral infections, severe acute pancreatitis, and rejection reactions to kidney transplants. A-SAA has greater clinical diagnostic value in patients who are immunosuppressed, patients with cystic fibrosis who are treated with corticoids, and preterm infants with late-onset sepsis. Nevertheless, for the assessment of the inflammation status and identification of viral infection in other pathologies, such as bacterial infections, the combinatorial use of A-SAA and other acute-phase proteins (APPs), such as CRP and procalcitonin (PCT), can provide more information and sensitivity than the use of any of these proteins alone, and the information generated is important in guiding antibiotic therapy. In addition, A-SAA-associated diseases and the diagnostic value of A-SAA are discussed. However, the relationship between different A-SAA isotypes and their human diseases are mostly derived from research laboratories with limited clinical samples. Thus, further clinical evaluations are necessary to confirm the clinical significance of each A-SAA isotype. Furthermore, the currently available A-SAA assays are based on polyclonal antibodies, which lack isotype specificity and are associated with many inflammatory diseases. Therefore, these assays are usually used in combination with other biomarkers in the clinic.


Assuntos
Reação de Fase Aguda , Doença , Inflamação/sangue , Inflamação/diagnóstico , Proteína Amiloide A Sérica/análise , Amiloidose/sangue , Amiloidose/diagnóstico , Amiloidose/metabolismo , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/metabolismo , Humanos , Inflamação/metabolismo , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/metabolismo , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/metabolismo , Proteína Amiloide A Sérica/metabolismo
19.
Mediators Inflamm ; 2019: 6518308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049027

RESUMO

The aim of the study was to evaluate the inflammatory reaction in children with pseudocroup and compare it with other laryngological diseases according to the available literature data. The study group included 51 children hospitalized because of pseudocroup. The measurements of the acute phase proteins (APP), such as C-reactive protein (CRP), alpha-1-antitrypsin (AT), alpha-1-antichymotrypsin (ACT), alpha-1-acid glycoprotein (AGP), ceruloplasmin (Cp), transferrin (Tf), alpha-2-macroglobulin (A2M), and haptoglobin (Hp) were obtained at 3 time points. The glycosylation profiles of AGP, ACT, and Tf were completed. An increased AGP level was observed in girls. The AGP glycosylation revealed the advantage of the W0 variant over the W1 variant. W1 and W2 were decreased in boys. W3 emerged in boys. The Tf concentration and T4 variant were lower compared to the control group. The A2M level was lower after treatment. The Hp and AT levels were decreased a few weeks later. The ACT glycosylation revealed a decrease of the A4 variant in boys. In conclusion, the inflammatory reaction during pseudocroup was of low intensity. The APP glycosylation suggested a chronic process. In a follow-up investigation, no normalization of the parameters was noted, but signs of persistent inflammation were observed.


Assuntos
Reação de Fase Aguda/metabolismo , Crupe/metabolismo , Laringite/metabolismo , Proteínas da Fase Aguda/metabolismo , Proteína C-Reativa/metabolismo , Ceruloplasmina/metabolismo , Haptoglobinas/metabolismo , Humanos , Orosomucoide/metabolismo , Transferrina/metabolismo , alfa 1-Antiquimotripsina/metabolismo , alfa 1-Antitripsina/metabolismo
20.
J Immunol ; 202(12): 3359-3369, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31076532

RESUMO

Haptoglobin (Hp), a type of acute-phase protein, is known to have a systemic anti-inflammatory function and to modulate inflammation by directly affecting immune cells, such as T cells, dendritic cells, and macrophages. However, the effects of Hp on osteoclast differentiation are not well studied, even though osteoclast precursor cells belong to a macrophage-monocyte lineage. In this study, we found that the bone volume was reduced, and the number of osteoclasts was increased in Hp-deficient mice compared with wild-type mice. Moreover, our in vitro studies showed that Hp inhibits osteoclastogenesis by reducing the protein level of c-Fos at the early phase of osteoclast differentiation. We revealed that Hp-induced suppression of c-Fos was mediated by increased IFN-ß levels. Furthermore, Hp stimulated IFN-ß via a TLR4-dependent mechanism. These results demonstrate that Hp plays a protective role against excessive osteoclastogenesis via the Hp-TLR4-IFN-ß axis.


Assuntos
Haptoglobinas/metabolismo , Interferon beta/metabolismo , Osteoclastos/fisiologia , Reação de Fase Aguda , Animais , Reabsorção Óssea/genética , Diferenciação Celular , Células Cultivadas , Haptoglobinas/genética , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteogênese , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transdução de Sinais
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