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1.
Sci Rep ; 8(1): 5620, 2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618729

RESUMO

During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2 -/- ) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR. AA amyloid deposition was suppressed in Apoa2 -/- mice compared with wild type (WT) mice. During APR, Apoa2 -/- mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2 -/- mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2 -/- mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2 -/- mice showed increases in LDL and very large HDL during APR. SAA was distributed more widely in lipoprotein particles ranging from chylomicrons to very small HDL in Apoa2 -/- mice. Our observations uncovered the critical roles of ApoA-II in inflammation, serum lipoprotein stability and AA amyloidosis morbidity, and prompt consideration of therapies for AA and other amyloidoses, whose precursor proteins are associated with circulating HDL particles.


Assuntos
Reação de Fase Aguda/fisiopatologia , Amiloidose/etiologia , Apolipoproteína A-II/fisiologia , Lipoproteínas HDL/sangue , Lipoproteínas HDL/química , Pneumonia/etiologia , Proteína Amiloide A Sérica/metabolismo , Reação de Fase Aguda/complicações , Amiloide/química , Amiloidose/patologia , Animais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Pneumonia/patologia , Proteína Amiloide A Sérica/genética
2.
J Neuroinflammation ; 14(1): 196, 2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28964257

RESUMO

BACKGROUND: Increased relapse rates in multiple sclerosis (MS) as a consequence of peripheral immune system activation, owing to infection for example, have been widely reported, but the mechanism remains unclear. Acute brain injury models can be exacerbated by augmenting the hepatic acute phase response (APR). Here, we explored the contribution of the hepatic APR to relapse in two rodent models of MS. METHODS: Mice with MOG-CFA-induced chronic relapsing experimental autoimmune encephalitis (CR-EAE) were killed before, during and after the first phase of disease, and the brain and liver chemokine, cytokine and acute phase protein (APP) mRNA expression profile was determined. During remission, the APR was reactivated with an intraperitoneal lipopolysaccharide (LPS) and clinical score was monitored throughout. To explore the downstream mediators, CXCL-1, which is induced as part of the APR, was injected into animals with a focal, cytokine/MOG-induced EAE lesion (fEAE) and the cellularity of the lesions was assessed. RESULTS: Compared to CFA control, in a rodent CR-EAE model, an hepatic APR preceded clinical signs and central cytokine production in the initial phase of disease. Compared to administration in naïve animals, an LPS challenge during the asymptomatic remission phase of CR-EAE rodents provoked relapse and resulted in the increased and extended expression of specific peripheral hepatic chemokines. CXCL-1 and several other APPs were markedly elevated. A single intravenous administration of the highly induced chemokine, CXCL-1, was found to be sufficient to reactivate the lesions by increasing microglial activation and the recruitment of T cells in fEAE lesions. CONCLUSIONS: The APR plays a contributing role to the pathology seen in models of chronic brain injury and in translating the effects of peripheral immune system stimulation secondary to trauma or infection into central pathology and behavioural signs. Further elucidation of the exact mechanisms in this process will inform development of more effective, selective therapies in MS that, by suppressing the hepatic chemokine response, may prevent relapse.


Assuntos
Reação de Fase Aguda/fisiopatologia , Encéfalo/metabolismo , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/fisiopatologia , Fígado/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Quimiocina CXCL1/administração & dosagem , Citocinas/genética , Modelos Animais de Doenças , Feminino , Adjuvante de Freund/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Camundongos , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/toxicidade , RNA Mensageiro , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/metabolismo , Fatores de Tempo
3.
Injury ; 48 Suppl 1: S10-S14, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28456367

RESUMO

Intramedullary nailing, as the gold standard stabilisation method of most long bones, has been tailed by its extensive use as the basic tool of investigating the immune response to trauma in many large and small animal models, as well as at the clinical setting. Over the last few decades a complex map of interactions between pro and anti-inflammatory pathways has been the result of these significant global research efforts. Parallel to the evolution of modern nailing and reaming techniques, significant developments at the fields of other disciplines relevant to trauma care, has improved the contemporary management of injured patients, challenging previous concepts and altering clinical barriers. The current article aims to summarise the current understanding of the effect of instrumenting the medullary canal after trauma, and hint on potential future directions.


Assuntos
Reação de Fase Aguda/fisiopatologia , Embolia Gordurosa/fisiopatologia , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas , Complicações Pós-Operatórias/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Fraturas da Tíbia/cirurgia , Reação de Fase Aguda/imunologia , Animais , Fenômenos Biomecânicos , Citocinas/metabolismo , Embolia Gordurosa/imunologia , Fraturas do Fêmur/imunologia , Fraturas do Fêmur/fisiopatologia , Fixação Intramedular de Fraturas/efeitos adversos , Consolidação da Fratura , Humanos , Complicações Pós-Operatórias/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Fraturas da Tíbia/imunologia , Fraturas da Tíbia/fisiopatologia
4.
J Arthroplasty ; 32(1): 309-314, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27554779

RESUMO

BACKGROUND: During surgery, trauma to musculoskeletal tissue induces a systemic reaction known as the acute phase response (APR). When excessive or prolonged, the APR has been implicated as an underlying cause of surgical complications. The purpose of this study was to determine the typical APR following total joint arthroplasty in a healthy population defined by the Charlson Comorbidity Index (CCI). METHODS: This retrospective study identified 180 healthy patients (CCI < 2) who underwent total joint arthroplasty by a single surgeon for primary osteoarthritis from 2013 to 2015. Serial measurements of C-reactive protein (CRP) and fibrinogen were obtained preoperative, perioperative, and at 2 and 6 weeks postoperative. RESULTS: Postoperative CRP peaked during the inpatient period and returned to baseline by 2 weeks. Fibrinogen peaked after CRP and returned to baseline by 6 weeks. Elevated preoperative CRP correlated with a more robust postoperative APR for both total hip arthroplasty and total knee arthroplasty, suggesting that a patient's preoperative inflammatory state correlates with the magnitude of the postoperative APR. CONCLUSION: Measurement of preoperative acute phase reactants may provide an objective means to predict a patient's risk of postoperative dysregulation of the APR and complications.


Assuntos
Reação de Fase Aguda/diagnóstico , Reação de Fase Aguda/fisiopatologia , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Quadril/cirurgia , Reação de Fase Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Proteína C-Reativa/análise , Feminino , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/fisiopatologia , Período Pós-Operatório , Estudos Retrospectivos
5.
Transl Res ; 182: 27-48, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27818230

RESUMO

The systemic response to ischemic stroke is associated with the hepatic acute phase response (APR) that modulates leukocytes recruitment to the injured brain. The inappropriate recruitment of leukocytes to the brain parenchyma can result in blood-brain barrier (BBB) breakdown. Emerging data suggest that peroxisome proliferator-activated receptor beta/delta (PPAR-ß/δ) activation has a potential neuroprotective role in ischemic stroke. However, mechanisms of PPAR-ß/δ mediated protection in ischemic insults remain unclear. In the present study, we determined for the first time, the effects of GW0742, a PPAR-ß/δ agonist on the APR following brain injury and assessed the effects on BBB permeability and tight junction integrity via claudin-5, occludin, and zona occludens-1 expression. C57/BL6 mice were exposed to 1 hour of ischemia and received 10 minutes before reperfusion either a vehicle solution or GW0742. Hepatic expression of chemokines (C-X-C motif ligand: CXCL1, CXCL2, and CXCL10), serum amyloid A-1, tumor necrosis factor alpha, interleukin-1ß, and interleukin-6 was measured, and the extent of brain and hepatic neutrophil infiltration was determined. The results showed that GW0742 treatment decreased infarct volume and edema, reactant production and neutrophil recruitment to the brain and liver, which is a hallmark of the APR. GW0742 significantly reduced BBB leakage and metalloproteinase 9 expression and upregulated the expression of tight junction proteins. These findings may help to guide the experimental and clinical therapeutic use of PPAR-ß/δ agonists against brain injury.


Assuntos
Reação de Fase Aguda/tratamento farmacológico , Barreira Hematoencefálica/patologia , Lesões Encefálicas/tratamento farmacológico , PPAR delta/agonistas , PPAR beta/agonistas , Tiazóis/uso terapêutico , Reação de Fase Aguda/complicações , Reação de Fase Aguda/fisiopatologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Edema Encefálico/complicações , Edema Encefálico/tratamento farmacológico , Edema Encefálico/patologia , Edema Encefálico/fisiopatologia , Infarto Encefálico/complicações , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/patologia , Infarto Encefálico/fisiopatologia , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Claudinas/genética , Claudinas/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Mediadores da Inflamação/metabolismo , Injeções Intraperitoneais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/efeitos dos fármacos , Ocludina/metabolismo , PPAR delta/genética , PPAR delta/metabolismo , PPAR beta/genética , PPAR beta/metabolismo , Permeabilidade/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tiazóis/administração & dosagem , Tiazóis/farmacologia , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
6.
PLoS One ; 11(10): e0164938, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27792729

RESUMO

Inflammation and activation of the acute phase response (APR) are energetically demanding processes that protect against pathogens. Phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) are antigens commonly used to stimulate inflammation and the APR, respectively. We tested the hypothesis that the APR after an LPS challenge was energetically more costly than the inflammatory response after a PHA challenge in the fish-eating Myotis bat (Myotis vivesi). We measured resting metabolic rate (RMR) after bats were administered PHA and LPS. We also measured skin temperature (Tskin) after the LPS challenge and skin swelling after the PHA challenge. Injection of PHA elicited swelling that lasted for several days but changes in RMR and body mass were not significant. LPS injection produced a significant increase in Tskin and in RMR, and significant body mass loss. RMR after LPS injection increased by 140-185% and the total cost of the response was 6.50 kJ. Inflammation was an energetically low-cost process but the APR entailed a significant energetic investment. Examination of APR in other bats suggests that the way in which bats deal with infections might not be uniform.


Assuntos
Reação de Fase Aguda/metabolismo , Quirópteros/imunologia , Metabolismo Energético/fisiologia , Inflamação/metabolismo , Reação de Fase Aguda/fisiopatologia , Animais , Metabolismo Basal/efeitos dos fármacos , Metabolismo Basal/fisiologia , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Quirópteros/metabolismo , Quirópteros/fisiologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Inflamação/fisiopatologia , Lipopolissacarídeos/farmacologia , Masculino , Fito-Hemaglutininas/farmacologia
7.
Neurochem Res ; 41(4): 748-57, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26498936

RESUMO

The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1ß, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.


Assuntos
Reação de Fase Aguda/prevenção & controle , Aminoácidos/uso terapêutico , Edema Encefálico/prevenção & controle , Hemorragias Intracranianas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Reação de Fase Aguda/metabolismo , Reação de Fase Aguda/fisiopatologia , Animais , Aquaporina 4/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/fisiopatologia , Claudina-5/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Hemorragias Intracranianas/metabolismo , Hemorragias Intracranianas/fisiopatologia , Masculino , Ocludina/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
8.
J Anim Sci ; 93(5): 2460-70, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26020341

RESUMO

Beef bull calves (n = 62) were assigned randomly, within sire breed, to 1 of 4 treatments at birth. Treatments were 1) surgical castration near birth, 2) surgical castration near birth with oral administration of meloxicam (1 mg/kg BW), 3) surgical castration at weaning (WNG), or 4) surgical castration at weaning with oral administration of meloxicam (1 mg/kg BW; WMX). A subset of calves (n = 7/treatment group) were selected randomly near birth for blood collection, behavioral analyses, and rectal temperature (RT) records for a 7-d postcastration period on d 0 (birth), 1, 3, and 7, and on d 214 (weaning), 214 + 6 h, 215, 217, 221, and 228. Calf standing and lying activity were monitored from the same subsets by recording x- and y-axis positions of an accelerometer attached to the right metatarsus for 7 d postcastration. Calf BW was recorded throughout the entire production cycle, and carcass data were collected at slaughter. For statistical analyses, bulls left intact at birth were considered a positive control (BUL) for observations that occurred before their treatment application at weaning; likewise, bulls castrated at birth were considered a negative control (STR) during postweaning observations. No difference (P > 0.88) occurred in ADG between treatments throughout the preweaning period (d 0 to 214); however, 56-d postweaning ADG was greatest ( P= 0.02) in STR, intermediate in WMX, and least in WNG. At weaning, haptoglobin (Hp) was greater (P ≤ 0.005) for WNG and WMX compared to STR on d 214+6 h, 215, and 217, and Hp was greater (P = 0.05) in WNG compared to WMX on d 217. Neutrophils increased (P < 0.001) and red blood cells decreased (P ≤ 0.03) for WNG and WMX on d 214+6 h and 217, respectively. Postweaning behavior observations indicated that STR calves spent the least proportion of time standing (P = 0.002) when compared to WNG and WMX. Furthermore, WMX calves exhibited a greater proportion of time spent standing (P = 0.03) compared to WNG. Grazing and finishing phase ADG and carcass measurements did not differ (P ≥ 0.24) across treatments. In this study, surgical castration at weaning, but not near birth, altered the acute phase response, behavior, and growth performance. Oral meloxicam reduced serum Hp and improved ADG briefly when administered to calves castrated at weaning. Oral administration of meloxicam may be efficacious for mitigating some of the stress and inflammation associated with castration of weaning-age bull calves.


Assuntos
Comportamento Animal/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Bovinos/crescimento & desenvolvimento , Orquiectomia/veterinária , Tiazinas/administração & dosagem , Tiazinas/farmacologia , Tiazóis/administração & dosagem , Tiazóis/farmacologia , Reação de Fase Aguda/fisiopatologia , Administração Oral , Fatores Etários , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Comportamento Animal/fisiologia , Composição Corporal/fisiologia , Peso Corporal/efeitos dos fármacos , Bovinos/fisiologia , Haptoglobinas/metabolismo , Inflamação/fisiopatologia , Masculino , Meloxicam , Orquiectomia/métodos , Fatores de Tempo
9.
Innate Immun ; 20(8): 888-96, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24217218

RESUMO

Activation of the innate immune system and acute phase response (APR) results in several responses that include fever, metabolic adaptations and changes in behavior. The APR can be modulated by many factors, with stress being the most common. An elevation of stress hormones for a short duration of time can be beneficial. However, elevation of stress hormones repeatedly or for an extended duration of time can be detrimental to the overall health and well-being of animals. The stress and APR responses can also be modulated by naturally-occurring variations, such as breed, gender, and temperament. These three natural variations modulate both of these responses, and can therefore modulate the ability of an animal to recover from a stressor or infection. Understanding that cattle have different immunological responses, based on naturally occurring variations such as these, may be the foundation of new studies on how to effectively manage cattle so that health is optimized and production is benefited.


Assuntos
Reação de Fase Aguda/imunologia , Reação de Fase Aguda/fisiopatologia , Bovinos/imunologia , Bovinos/fisiologia , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia , Reação de Fase Aguda/genética , Reação de Fase Aguda/psicologia , Animais , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Temperamento
10.
J Dairy Sci ; 96(9): 5712-22, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23831090

RESUMO

In this study we examined the relationship between cortisol and inflammatory status in early lactating dairy cows after a stimulation test of the adrenal cortex. Twenty-four cows were grouped into quartiles (6 cows per each quartile) in accordance with the liver activity index (based on plasma concentration of negative acute phase proteins in early lactation); the quartiles were lower (LO; cows with the lowest liver functionality), intermediate lower, intermediate upper, and upper (UP; cows with the highest liver functionality). Each cow was injected i.v. with 20 µg of a synthetic analog of ACTH at 35 d in milk (DIM). Blood samples were taken to assess inflammatory status, and at 0, 30, and 60 min after ACTH challenge to measure total cortisol. The free cortisol fraction was analyzed in the LO and UP quartiles and the bound cortisol fraction was estimated as the difference between total and free cortisol. The LO, in comparison with the other quartiles, suffered a more severe inflammatory status, with the highest values of haptoglobin, reactive oxygen metabolites, and total nitric oxide metabolites and the lowest concentration of direct or indirect markers of negative acute phase proteins. The cows in the LO quartile had the highest values of plasma nonesterified fatty acids and ß-hydroxybutyrate at 7 DIM, suggesting a more severe body lipid mobilization. The LO quartile cows showed the highest frequency of health problems and the lowest milk yield in the first 35 DIM. Thirty minutes after the ACTH treatment, the concentration of total cortisol was lower in LO in comparison to other groups. Similarly, the bound cortisol fraction was lower in LO versus UP. The adrenal response appeared inversely related with health status after calving (e.g., lower in LO cows, experiencing the most severe inflammatory status). The lower increase in cortisol after the ACTH challenge in cows with greater inflammation (LO quartile) seems a consequence of the lower availability of cortisol-binding globulin synthetized by the liver, but other mechanisms can be involved (e.g., rate of cortisol production, secretion, and metabolic clearance). Our data provide evidence that inflammation and metabolic changes reduce the concentration of circulating plasma cortisol during an acute stress. Hence, the acute phase response in dairy cows should be taken into account to interpret the results obtained from stimulation tests of the adrenal cortex.


Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Hidrocortisona/sangue , Inflamação/fisiopatologia , Lactação/fisiologia , Fígado/fisiologia , Reação de Fase Aguda/fisiopatologia , Animais , Bovinos , Doenças dos Bovinos , Feminino , Hidrocortisona/fisiologia , Lactação/efeitos dos fármacos , Fígado/efeitos dos fármacos
11.
Eur J Appl Physiol ; 113(8): 2159-66, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23615823

RESUMO

We tested the hypothesis that acute inflammation may cause arterial stiffening in older adults. We further explored if high cardiorespiratory fitness may partially prevent the unfavorable effect of arterial stiffening produced by acute systemic inflammation in older adults. Using a randomized double-blind sham placebo-controlled design, forty healthy older adults were assigned to receive either an influenza vaccine or a sham vaccine. C-reactive protein and interleukin 6 (IL-6) were measured as markers of inflammation. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIX) as indices of arterial stiffness and wave reflection were assessed at baseline and 24 and 48 h after each vaccination. When compared with sham placebo, the influenza vaccination caused a significant increase in CRP (p < 0.05) and IL-6 (p < 0.05). Carotid-femoral PWV, but not AIX was significantly increased after influenza vaccination (p < 0.05), but not sham vaccination. The high cardiorespiratory fitness group had an attenuated increase in PWV as compared to the low cardiorespiratory fitness group after acute inflammation (p < 0.05). These findings show that acute inflammation may cause significant increases in arterial stiffness in older adults, but these increases were attenuated in the high cardiorespiratory fitness group as compared to the low cardiorespiratory fitness group.


Assuntos
Reação de Fase Aguda/fisiopatologia , Frequência Cardíaca , Consumo de Oxigênio , Aptidão Física , Rigidez Vascular , Reação de Fase Aguda/etiologia , Fatores Etários , Idoso , Proteína C-Reativa/análise , Artérias Carótidas/fisiopatologia , Método Duplo-Cego , Teste de Esforço , Feminino , Artéria Femoral/fisiopatologia , Humanos , Vacinas contra Influenza/imunologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Vacinação/efeitos adversos
12.
Eur J Clin Invest ; 43(5): 510-21, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23489139

RESUMO

Exacerbations of chronic obstructive respiratory disease (ECOPD) are acute events characterized by worsening of the patient's respiratory symptoms, particularly dyspnoea, leading to change in medical treatment and/or hospitalisation. AECOP are considered respiratory diseases, with reference to the respiratory nature of symptoms and to the involvement of airways and lung. Indeed respiratory infections and/or air pollution are the main causes of ECOPD. They cause an acute inflammation of the airways and the lung on top of the chronic inflammation that is associated with COPD. This acute inflammation is responsible of the development of acute respiratory symptoms (in these cases the term ECOPD is appropriate). However, the acute inflammation caused by infections/pollutants is almost associated with systemic inflammation, that may cause acute respiratory symptoms through decompensation of concomitant chronic diseases (eg acute heart failure, thromboembolism, etc) almost invariably associated with COPD. Most concomitant chronic diseases share with COPD not only the underlying chronic inflammation of the target organs (i.e. lungs, myocardium, vessels, adipose tissue), but also clinical manifestations like fatigue and dyspnoea. For this reason, in patients with multi-morbidity (eg COPD with chronic heart failure and hypertension, etc), the exacerbation of respiratory symptoms may be particularly difficult to investigate, as it may be caused by exacerbation of COPD and/or ≥ comorbidity, (e.g. decompensated heart failure, arrhythmias, thromboembolisms) without necessarily involving the airways and lung. In these cases the term ECOPD is inappropriate and misleading.


Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Reação de Fase Aguda/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Inflamação/fisiopatologia , Índice de Gravidade de Doença
13.
J Comp Physiol B ; 183(3): 297-312, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23160839

RESUMO

While fever is known to occur in invertebrates and vertebrates, the mechanisms of fever in animals other than mammals have received scant attention. We look initially at the recognition, by the avian immune system, of pathogen associated molecular patterns and the likely role of toll-like receptors in signaling the presence of bacteria and viruses. Several mediators of fever are subsequently released by immune cells, including interleukin-6 and interleukin-1ß, that eventually reach the brain and alter thermoregulatory function. As is the case in mammals, prostaglandins appear to be the ultimate mediators of fever in birds, since the febrile response is attenuated when prostaglandin synthesis is inhibited. Ambient temperature modulates the fever response, with larger fevers at higher, and smaller fevers at lower ambient temperatures. Glucocorticoid levels are increased during fever and seem to play an important role by modulating the extent of fever generation, possibly playing a role in the attenuation of fever after repeated exposure to a pathogen in a process termed tolerance, suggesting that the fever process can be phenotypically adapted to likely future conditions. While fever has an ancient phylogenetic history and many of the underling mechanisms in birds appear similar to mammals, there are several important differences that suggest fever has evolved quite differently in these two homeothermic classes.


Assuntos
Reação de Fase Aguda/veterinária , Doenças das Aves/imunologia , Doenças das Aves/fisiopatologia , Febre/veterinária , Prostaglandinas/metabolismo , Receptores Toll-Like/metabolismo , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/fisiopatologia , Fatores Etários , Animais , Aves , Temperatura Corporal , Ritmo Circadiano/fisiologia , Citocinas/metabolismo , Febre/imunologia , Febre/fisiopatologia , Glucocorticoides/metabolismo , Óxido Nítrico/metabolismo , Temperatura
14.
PLoS One ; 7(8): e44191, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22952923

RESUMO

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.


Assuntos
Reação de Fase Aguda/fisiopatologia , Temperatura Corporal/efeitos dos fármacos , Encéfalo/fisiopatologia , Ácido Glutâmico/toxicidade , Neurotoxinas/toxicidade , Acidente Vascular Cerebral/fisiopatologia , Reação de Fase Aguda/sangue , Reação de Fase Aguda/patologia , Animais , Metabolismo Basal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Ácido Glutâmico/sangue , Hipotermia Induzida , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Interleucina-6/sangue , Imagem por Ressonância Magnética , Masculino , Neurotoxinas/sangue , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia
15.
Q Rev Biol ; 87(1): 3-18, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22518930

RESUMO

The acutephase response (APR) is a systemic response to severe trauma, infection, and cancer, although many of the numerous cytokine-mediated components of the APR are incompletely understood. Some of these components, such as fever, reduced availability of iron and zinc, and nutritional restriction due to anorexia, appear to be stressors capable of causing harm to both the pathogen and the host. We review how the host benefits from differences in susceptibility to stress between pathogens and the host. Pathogens, infected host cells, and neoplastic cells are generally more stressed or vulnerable to additional stress than the host because: (a) targeted local inflammation works in synergy with APR stressors; (b) proliferation/growth increases vulnerability to stress; (c) altered pathogen physiology results in pathogen stress or vulnerability; and (d) protective heat shock responses are partially abrogated in pathogens since their responses are utilized by the host to enhance immune responses. Therefore, the host utilizes a coordinated system of endogenous stressors to provide additional levels of defense against pathogens. This model of immune brinksmanship can explain the evolutionary basis for the mutually stressful components of the APR.


Assuntos
Reação de Fase Aguda/fisiopatologia , Interações Hospedeiro-Patógeno , Imunidade Inata , Estresse Fisiológico , Animais , Humanos
16.
Domest Anim Endocrinol ; 43(2): 146-53, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22425434

RESUMO

Although livestock experience many stressors throughout their life, one of the most commonly experienced, and most difficult to control, is stress caused by fluctuations in environmental temperatures that extend beyond the thermoneutral (TN) zone for an animal. In swine, cold stress has long been recognized as a main cause of neonatal morbidity and mortality. A possible explanation for this increased morbidity and mortality may be related to their inability to generate a febrile response. Previously, we reported that the acute phase immune response, including the generation of fever, after exposure to lipopolysaccharide (LPS; Escherichia coli O111: B4; Sigma-Aldrich, St Louis, MO, USA) is substantially altered in neonatal pigs maintained in a cold environment (ie, 18°C). Neonatal pigs that were maintained in a cold environment and administered LPS experienced a period of hypothermia coupled with altered endocrine and proinflammatory cytokine responses that could prove detrimental. In cattle, we previously reported differences in the acute phase immune response of two diverse breeds of Bos taurus cattle (Angus and Romosinuano) when maintained under TN conditions and exposed to LPS. More recently we have reported that differences in the stress and immune responses of Angus and Romosinuano heifers varies, depending on whether the cattle were housed at either TN or heat stress air temperatures. Our data clearly show that even intermittent periods of heat stress similar to that experienced in production environments can have significant effects on the stress and innate immune responses of cattle. Understanding the effect of thermal stress on livestock is critical to developing and implementing alternative management practices to improve their overall health and well-being.


Assuntos
Lipopolissacarídeos/administração & dosagem , Gado/imunologia , Gado/fisiologia , Temperatura , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/fisiopatologia , Animais , Animais Recém-Nascidos/imunologia , Animais Recém-Nascidos/fisiologia , Bovinos , Temperatura Baixa , Meio Ambiente , Escherichia coli , Febre , Temperatura Alta , Estresse Fisiológico/imunologia , Estresse Fisiológico/fisiologia , Suínos
17.
Amino Acids ; 42(2-3): 473-84, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21814792

RESUMO

Bacterial lipopolysaccharide (LPS) is an effective activator of the components of innate immunity. It has been shown that polyamines and their metabolic enzymes affect the LPS-induced immune response by modulating both pro- and anti-inflammatory actions. On the other hand, LPS causes changes in cellular polyamine metabolism. In this study, the LPS-induced inflammatory response in spermidine/spermine N(1)-acetyltransferase overexpressing transgenic mice (SSAT mice) was analyzed. In liver and kidneys, LPS enhanced the activity of the polyamine biosynthetic enzyme ornithine decarboxylase and increased the intracellular putrescine content in both SSAT overexpressing and wild-type mice. In survival studies, the enhanced polyamine catabolism and concomitantly altered cellular polyamine pools in SSAT mice did not affect the LPS-induced mortality of these animals. However, in the acute phase of LPS-induced inflammatory response, the serum levels of proinflammatory cytokines interleukin-1ß and interferon-γ were significantly reduced and, on the contrary, anti-inflammatory cytokine interleukin-10 was significantly increased in the sera of SSAT mice compared with the wild-type animals. In addition, hepatic acute-phase proteins C-reactive protein, haptoglobin and α(1)-acid glycoprotein were expressed in higher amounts in SSAT mice than in the wild-type animals. In summary, the study suggests that SSAT overexpression obtained in SSAT mice enhances the anti-inflammatory actions in the acute phase of LPS-induced immune response.


Assuntos
Acetiltransferases/metabolismo , Reação de Fase Aguda/induzido quimicamente , Lipopolissacarídeos/farmacologia , Acetiltransferases/genética , Reação de Fase Aguda/enzimologia , Reação de Fase Aguda/fisiopatologia , Animais , Sequência de Bases , Citocinas/metabolismo , Primers do DNA , Camundongos , Taxa de Sobrevida
19.
Nat Rev Rheumatol ; 7(5): 282-9, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21468143

RESUMO

Measurement of serum C-reactive protein (CRP) level is in widespread clinical use as a sensitive marker of inflammation. CRP has a role in the clearance of bacteria and of dying and altered cells, and might also have more complex immunomodulatory functions. Impaired clearance of apoptotic cells is important in the pathogenesis of systemic lupus erythematosus (SLE), raising the possibility that CRP dysregulation plays a part in this process. We review the available functional and genetic evidence supporting a role for CRP in the pathogenesis of SLE, but recognize that inconsistencies in the existing data mean that conclusions have to be interpreted with caution. More consistent is the evidence that the genetic variants influencing basal CRP level also influence the magnitude of the acute-phase rise in CRP level in active inflammation. Initial reports suggest that these genetic effects might be large enough to directly influence clinical decision-making processes that are based on an interpretation of CRP thresholds. This concept is explored further in this article, particularly in relation to the use of the CRP-based disease activity score in the evaluation of rheumatoid arthritis, where a systematic under-scoring or over-scoring of disease activity could result from a failure to consider the genetic influences on CRP level.


Assuntos
Proteína C-Reativa/genética , Proteína C-Reativa/fisiologia , Doenças Reumáticas/genética , Doenças Reumáticas/fisiopatologia , Reação de Fase Aguda/sangue , Reação de Fase Aguda/fisiopatologia , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Biomarcadores/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/fisiopatologia , Doenças Reumáticas/sangue , Índice de Gravidade de Doença
20.
Am J Physiol Regul Integr Comp Physiol ; 300(6): R1418-25, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21346241

RESUMO

Pathogens may induce different immune responses in hosts contingent on pathogen characteristics, host characteristics, or interactions between the two. We investigated whether the broadly effective acute-phase response (APR), a whole body immune response that occurs in response to constitutive immune receptor activation and includes fever, secretion of immune peptides, and sickness behaviors such as anorexia and lethargy, varies with pathogen identity in the house sparrow (Passer domesticus). Birds were challenged with a subcutaneous injection of either a glucan at 0.7 mg/kg (to simulate fungal infection), a synthetic double-stranded RNA at 25 mg/kg (to simulate viral infection), or LPS at 1 mg/kg (to simulate a gram-negative bacterial infection), and then body mass, core body temperature changes, sickness behaviors, and secretion of an acute-phase protein, haptoglobin, were compared. Despite using what are moderate-to-high pyrogen doses for other vertebrates, only house sparrows challenged with LPS showed measurable APRs. Febrile, behavioral, and physiological responses to fungal and viral mimetics had minimal effects.


Assuntos
Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/fisiopatologia , Pirogênios/efeitos adversos , Pardais/fisiologia , Proteínas da Fase Aguda/metabolismo , Animais , Índice de Massa Corporal , Temperatura Corporal/fisiologia , Modelos Animais de Doenças , Glucanos/efeitos adversos , Haptoglobinas/metabolismo , Lipopolissacarídeos/efeitos adversos , RNA de Cadeia Dupla/efeitos adversos
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