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1.
Respir Med ; 221: 107481, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38035945

RESUMO

INTRODUCTION: Behcet's disease (BD) is a chronic inflammatory disorder with arterial vasculitis. Although, pulmonary artery aneurysm (PAA) is accepted as the prototypic arterial disorder, an increasing presence of pulmonary artery thrombosis (PAT) with or without aneurysms was also reported in recent studies. In this study, we aimed to describe computed tomography pulmonary angiography (CTPA) findings of pulmonary involvement and its correlation with symptoms and acute phase response in BD. METHOD: In this retrospective study, 153 CTPA of BD patients were assessed by two radiologists. Clinical and laboratory data were collected from the patient files. Pulmonary artery involvement (PAI) was defined as thrombus or aneurysm in CT angiography. RESULTS: Most of (85.6 %) our patients were male and median age was 33.7 ± 10 years during angiographic assessments. Sixty-two (40.5 %) angiographies presented a thrombus: 14 subsegmental, 29 segmental, 13 lobar and 6 main branches. Among these, 82.3 % (n = 51) had bilateral involvement. Isolated PAT was present in 58 (93.5 %) angiographies with only 4 (2.6 %) angiographies displaying an aneurysm together with a thrombus. Pulmonary infarction was detected in 9 angiographies. Forty-four (29.3 %) patients, almost all of them under immunosuppressive treatments for other indications, were screened for asymptomatic pulmonary involvement (without any symptoms or increased acute-phase response (APR)), and one fourth of these were diagnosed as having a segmental or subsegmental PAT. CONCLUSION: Our results show that isolated pulmonary thrombosis is the main form of PAI, and isolated pulmonary aneurysm formation is rare in our BD cases. In the presence of pulmonary symptoms with or without increased APRs, involvement of segmental or more proximal parts of pulmonary arteries is most commonly detected. We also observed that PAI may be seen in about one fourth of especially male BD patients without symptoms or increased APR. Our results suggest that BD patients with pulmonary symptoms should be screened by CTPA for PAI, however, further research is needed to clarify the role of routine CTPA screening in asymptomatic BD patients.


Assuntos
Aneurisma , Síndrome de Behçet , Hipertensão Pulmonar , Pneumopatias , Trombose , Humanos , Masculino , Adulto Jovem , Adulto , Feminino , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Artéria Pulmonar/diagnóstico por imagem , Reação de Fase Aguda , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Angiografia , Aneurisma/diagnóstico por imagem , Aneurisma/etiologia , Trombose/diagnóstico por imagem , Trombose/etiologia
2.
Schizophr Res ; 264: 122-129, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128343

RESUMO

BACKGROUND: Several studies have indicated that the plasma concentration of risperidone increases 3-5-fold during the acute-phase reaction (APR) of inflammation or infection. Psychiatric symptoms are present or deteriorate when the dose is lowered; thus, the complex effects of inflammation on the pharmacokinetics of risperidone need to be examined. METHODS: We established a APR model in rabbits induced by lipopolysaccharide (LPS) and studied the effect of APR on pharmacokinetics, distribution and disposition of risperidone in vivo and in vitro. RESULTS: Following intramuscular administration, the plasma exposures for risperidone and its active metabolite (9-hydroxyrisperidone) were increased approximately 6-fold on day 2 of inflammation. The exposure values did not change between day 2 and 5 of inflammation, nor did the metabolite-to-parent ratio before and during inflammation. Following oral administration, the increase of risperidone exposure was twice as high as that following intramuscular administration during APR. However, the concentration of risperidone and 9-hydroxyrisperidone in brain tissue was similar between the inflammatory and control groups. Moreover, the plasma protein binding (PPB) of risperidone and 9-hydroxyrisperidone associated with inflammation were all increased to >99 %. In addition, risperidone and 9-hydroxyrisperidone were not substrates of the key transporters, OATP1B3, OCT2, OAT3, MATE-1, or MATE-2 K. The expression of progesterone X receptor and P-glycoprotein was inhibited by LPS. CONCLUSION: During APR, reduced expression of P-glycoprotein and increased PPB were responsible for increased exposure in plasma, while maintaining stable concentrations in the brain, and risperidone does not need to be dose-adjusted so as to achieve psychopharmacological outcomes.


Assuntos
Antipsicóticos , Risperidona , Animais , Coelhos , Palmitato de Paliperidona , Isoxazóis/farmacocinética , Pirimidinas/farmacocinética , Reação de Fase Aguda/induzido quimicamente , Lipopolissacarídeos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP
3.
PeerJ ; 11: e16590, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107577

RESUMO

Background: The pathological mechanism of heat stroke (HS) involves the acute phase response, unbalanced immunological/inflammatory reactions, and coagulation initiation, especially platelet activation. Although exosomes contain proteins involved in these biological processes, their protein cargo levels and potential roles in HS remain unknown. This study explored the serum exosome protein expression patterns after HS and their potential roles in the pathogenesis of HS. Methods: Blood samples were collected from ten patients diagnosed with HS upon admission to the intensive care unit (six with severe HS and four with mild HS). Samples from six healthy volunteers were included as control. Using ultracentrifugation, exosomes were prudently isolated, and their protein contents were profiled using liquid chromatography-tandem mass spectrometry analysis with isobaric tags for relative and absolute quantification-based proteomics. Results: Compared with healthy volunteers, patients with HS showed significant changes in the levels of 33 exosomal proteins (23 upregulated and 10 downregulated). The most upregulated proteins included serum amyloid A-1 (SAA-1), von Willebrand factor (vWF), S100A8, and histone H3. In addition, SAA-1, vWF, platelet membrane glycoprotein, S100A8, and histone H3 were more enriched in the exosomes from patients with severe HS than from those with mild HS. Gene ontology analysis revealed that the HS-modulated exosomal proteins were mostly related to inflammatory response, including the acute-phase response, platelet activation/degranulation, and innate immune response. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significant enrichment of proteins in the IL-17 signaling pathway, platelet activation, neutrophil extracellular trap formation, Fc epsilon RI signaling pathway, chemokine signaling pathway, and NOD-like receptor signaling pathway, among others. Several serum exosomal proteins, including SAA-1, vWF, and S100A8, which are related to the acute phase, inflammatory response, and platelet activation, were confirmed to be elevated in patients with HS, and were significantly correlated with disease severity, organ dysfunction, and death. Conclusion: Overall, this study explores the potential role of the serum exosomal proteome in the inflammatory response and platelet activation in HS, suggests the pathological mechanisms underlying HS-induced injuries, and recommends reliable exosomal biomarkers for predicting HS prognosis.


Assuntos
Exossomos , Golpe de Calor , Insolação , Humanos , Reação de Fase Aguda/metabolismo , Histonas/análise , Exossomos/química , Fator de von Willebrand/análise , Proteômica/métodos , Proteínas Sanguíneas/análise , Ativação Plaquetária , Golpe de Calor/metabolismo
5.
Fish Physiol Biochem ; 49(6): 1339-1355, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971553

RESUMO

The present study was executed to evaluate the effect of photoperiod on serum biochemical parameters (glucose, cortisol, ALT, AST and LDH), electrolytic balance (Sodium and potassium), acute phase response (CRP) and histopathology (liver, kidney and skin) of an endangered high valued catfish, Ompok bimaculatus. Catfish (21.00 ± 1.53 cm and 30.00 ± 2.31 g) from the acclimatized stock were randomly distributed to six 120 × 45 × 60 cm3 FRP tanks (n = 20 fish per tank) and exposed to 1500 lx light intensity under different photoperiods [24:0 light: dark (L: D), 15L: 9D, 12L: 12D, 9L: 15D, 0L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of bodyweight, twice a day for 60 days. Serum glucose, cortisol and enzymes including aspartate transaminase (AST), lactate dehydrogenase (LDH), alanine transaminase (ALT), and acute phase reactant, such as C-reactive protein (CRP) increased significantly (P < 0.05) in continuous light (24L: 0D), continuous dark (0L: 24D) and short day (9L: 15D) photoperiods, whereas in 15L: 9D and 12L:12D photoperiods, those were in decreasing trend. Serum electrolytes, i.e. potassium level was elevated and sodium level was declined in 24L: 0D, 0L: 24D and 9L: 15D photoperiod groups. Moreover, significant histological alterations in the liver, kidney and skin tissue were also evidenced in the experimented catfish. Typical polygonal hepatocytes with normal blood vessels in liver and normal organization of kidney were seen in catfish of 15L: 9D group. Histological analysis of other groups displayed nuclear degeneration, karyorrhexis, karyolysis, melanomacrophages, nuclear hypertrophy, sinusoid dilation and vacuolar degeneration in liver and hyaline droplets accumulation, granular degeneration, fragmentation of glomerulus and focal necrosis of epithelial cells in kidney. Additionally, general structure of the skin was observed in control group as well as in 15L: 9D group. Contrarily, in 24L: 0D group increased number of mucous cells and vacuoles was observed in the skin of butter catfish. In 9L: 15D and 0L: 24D photoperiods, O. bimaculatus exhibited ruptured epithelial cells, enlarged alarm cells, fat cells, necrotic cells and vacuoles in the skin tissue. The present study depicted that 15L: 9D photoperiod can induce better health of catfish, O. bimaculatus, which, in turn, can help farmers to increase the production of this high valued catfish in future.


Assuntos
Peixes-Gato , Fotoperíodo , Animais , Reação de Fase Aguda , Hidrocortisona , Glucose , Potássio , Sódio
6.
Front Immunol ; 14: 1207746, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022578

RESUMO

The development of cachexia in the setting of cancer or other chronic diseases is a significant detriment for patients. Cachexia is associated with a decreased ability to tolerate therapies, reduction in ambulation, reduced quality of life, and increased mortality. Cachexia appears intricately linked to the activation of the acute phase response and is a drain on metabolic resources. Work has begun to focus on the important inflammatory factors associated with the acute phase response and their role in the immune activation of cachexia. Furthermore, data supporting the liver, lung, skeletal muscle, and tumor as all playing a role in activation of the acute phase are emerging. Although the acute phase is increasingly being recognized as being involved in cachexia, work in understanding underlying mechanisms of cachexia associated with the acute phase response remains an active area of investigation and still lack a holistic understanding and a clear causal link. Studies to date are largely correlative in nature, nonetheless suggesting the possibility for a role for various acute phase reactants. Herein, we examine the current literature regarding the acute phase response proteins, the evidence these proteins play in the promotion and exacerbation of cachexia, and current evidence of a therapeutic potential for patients.


Assuntos
Caquexia , Neoplasias , Humanos , Caquexia/etiologia , Caquexia/metabolismo , Reação de Fase Aguda/metabolismo , Qualidade de Vida , Inflamação/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Proteínas de Fase Aguda
7.
Res Vet Sci ; 165: 105055, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37862863

RESUMO

Parasitic blood diseases (theileriosis, babesiosis, anaplasmosis, and trypanosomiasis) are common in regions where the distributions of the hosts, parasites, and vectors are convergent. They endanger animal production, and a few are also harmful to public health. The acute phase reaction (APR) is a complex, non-specific reaction that occurs in various events, including surgical trauma, infection, stress, inflammation, and neoplasia. To understand pathogenesis, we must study APR effects and acute phase proteins (APPs) alterations in naturally occurring and experimental infections. The elevation of haptoglobin (Hp), Serum amyloid A (SAA), and fibrinogen concentrations was markedly significant in bovine and ovine theileriosis. Hp, SAA, ceruloplasmin, and fibrinogen concentrations in anaplasmosis were dramatically elevated. A significant increase in SAA was observed in bovine babesiosis, while ovine babesiosis showed a significant rise in sialic acid levels. In cases of trypanosomiasis caused by T. vivax, there have been reports of elevated levels of Hp, complement C3, and antitrypsin. Improving our understanding of APR could result in more effective methods for diagnosis, treatment, control, and eradication of diseases. The article provides an overview of APPs alterations and other inflammation-related parameters (some cytokines, adenosine deaminase, and sialic acids) in parasitic blood diseases of ruminants.


Assuntos
Anaplasmose , Babesiose , Doenças dos Bovinos , Doenças Hematológicas , Parasitos , Doenças dos Ovinos , Theileriose , Tripanossomíase , Animais , Ovinos , Bovinos , Reação de Fase Aguda/veterinária , Babesiose/parasitologia , Proteína Amiloide A Sérica/metabolismo , Ruminantes , Haptoglobinas/metabolismo , Fibrinogênio , Tripanossomíase/veterinária , Doenças Hematológicas/veterinária
8.
J Dairy Sci ; 106(12): 9879-9891, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37678770

RESUMO

The availability of certain macronutrients is likely to influence the capacity of the immune system. Therefore, we investigated the acute phase response to intramammary (i.mam.) lipopolysaccharide (LPS) in dairy cows fed a nitrogenic diet (n = 10) high in crude protein, a glucogenic diet (n = 11) high in carbohydrates and glucogenic precursors, or a lipogenic diet (n = 11) high in lipids. Thirty-two dairy cows were fed one of the dietary concentrates directly after calving until the end of trial at 27 ± 3 days in milk (mean ± standard deviation). In wk 3 of lactation, 20 µg of LPS was i.mam. injected in one quarter, and sterile NaCl (0.9%) in the contralateral quarter. Milk samples of the LPS-challenged and control quarter were taken hourly from before (0 h) until 9 h after LPS challenge and analyzed for milk amyloid A (MAA), haptoglobin (HP), and IL-8. In addition, blood samples were taken in the morning, and composite milk samples at morning and evening milkings, from 1 d before until 3 d after LPS challenge, and again on d 9, to determine serum amyloid A (SAA) and HP in blood, and MAA and HP in milk. The mRNA abundance of various immunological and metabolic factors in blood leukocytes was quantified by quantitative reverse-transcription PCR from samples taken at -18, -1, 6, 9, and 23 h relative to LPS application. The dietary concentrates did not affect any of the parameters in blood, milk, and leukocytes. The IL-8 was increased from 2 h, HP from 2 to 3 h, and MAA from 6 h relative to the LPS administration in the milk of the challenged quarter and remained elevated until 9 h. The MAA and HP were also increased at 9 h after LPS challenge in whole-udder composite milk, whereas HP and SAA in blood were increased only after 23 h. All 4 parameters were decreased again on d 9. Similar for all groups, the mRNA abundance of HP and the heat shock protein family A increased after the LPS challenge, whereas the mRNA expression of the tumor necrosis factor α and the leukocyte integrin ß 2 subunit (CD18) were decreased at 6 h after LPS challenge. The glucose transporter (GLUT)1 mRNA abundance decreased after LPS, whereas that of the GLUT3 increased, and that of the GLUT4 was not detectable. The mRNA abundance of GAPDH was increased at 9 h after LPS and remained elevated. The acute phase protein response was detected earlier in milk compared with blood indicating mammary production. However, immunological responses to LPS were not affected by the availability of specific macronutrients provided by the different diets.


Assuntos
Doenças dos Bovinos , Mastite , Feminino , Bovinos , Animais , Lipopolissacarídeos/farmacologia , Reação de Fase Aguda/metabolismo , Reação de Fase Aguda/veterinária , Interleucina-8/metabolismo , Lactação/fisiologia , Leite/metabolismo , Dieta/veterinária , Glucose/metabolismo , Proteína Amiloide A Sérica/metabolismo , Mastite/metabolismo , Mastite/veterinária , RNA Mensageiro/metabolismo , Doenças dos Bovinos/metabolismo
9.
J Dairy Sci ; 106(12): 9807-9821, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641328

RESUMO

We examined the effects of a supplement of plant polyphenols extracts of green tea, capsicum, and fenugreek, and electrolytes ([Na+, K+]; AXT, Axion ThermoPlus, CCPA, France] during summer heat load on production, welfare, and oxidative stress proteins in adipose tissue (AT) of dairy cows. A total of 42 multiparous mid-lactation cows were divided into 3 groups during summer, and were fed for 2 wk either a standard milking cow diet (CTL, n = 14) or diets supplemented with 100 g/d of AXT (100AXT, n = 14), or 150 g/d of AXT (150AXT, n = 14), while being cooled 5 times a day. Then, half of the cows from each dietary treatment were cooled (CL) or not cooled (NCL) for 2 wk, after which the cooled and uncooled groups were switched for additional 2 wk. Cows were milked 3 times a day, and milk composition was analyzed at the end of each 2-wk period. Vaginal temperature (VT) was measured for 3 consecutive days in each period. Biopsies of subcutaneous AT were taken from 10 NCL cows (5 each of CTL and 150AXT) at the end of the period and examined by liquid chromatography-tandem mass spectrometry proteomics analysis. Data were analyzed with PROC MIXED of SAS (version 9.2, SAS Institute Inc.). The model included the effects of dietary treatment, cooling regimen, period, and their interactions. Protein and mRNA abundances and proteomic data (P ≤ 0.05 and fold change [FC] ± 1.5) were analyzed by t-test. Milk yields and 4% fat-corrected milk (FCM) were higher in 100AXT than in CTL; milk components were not different. Dry matter intake (DMI) was higher in 100AXT than in CTL. The effect of cooling and the interactions of period × cooling were significant for DMI, 4% FCM, energy-corrected milk, and milk/DMI. The proportion of time that VT was >39°C was lower in 100AXT and in 150AXT than in CTL. Daily rumination time was greater in 150AXT than in CTL, and lying time was greater in 100AXT and 150AXT than in CTL. Proteomics of AT demonstrated that 150AXT had increased abundances of peroxidasin (FC = 1.6), microsomal glutathione S-transferase 2 (FC = 2.5), and heme oxygenase 1 (FC = 3.6) compared with CTL. Top enriched canonical pathways included acute phase response signaling, Nrf2-mediated oxidative stress response, and lipopolysaccharide (LPS)/IL-1-mediated inhibition of RXR function. Immunoblots of AT showed a higher abundance of the transient receptor potential vanilloid 1 and of LPS binding protein in AT of 150AXT compared with CTL. Supplementation of AXT increased DMI, milk, and 4% FCM, lowered VT, improved welfare indices, and enriched the AT with Nrf2-oxidative stress response and acute phase response proteins in heat-stressed dairy cows.


Assuntos
Doenças dos Bovinos , Fator 2 Relacionado a NF-E2 , Animais , Bovinos , Feminino , Reação de Fase Aguda/metabolismo , Reação de Fase Aguda/veterinária , Tecido Adiposo/metabolismo , Doenças dos Bovinos/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Temperatura Alta , Lactação/fisiologia , Lipopolissacarídeos/metabolismo , Leite/química , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteômica
10.
Int J Mol Sci ; 24(14)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37511109

RESUMO

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".


Assuntos
Infecções Bacterianas , Proteína C-Reativa , Ferritinas , Inflamação , Humanos , Proteínas de Fase Aguda/metabolismo , Reação de Fase Aguda , Bactérias/metabolismo , Infecções Bacterianas/complicações , Biomarcadores , Proteína C-Reativa/metabolismo , Ferritinas/sangue , Inflamação/sangue , Inflamação/complicações
11.
J Dairy Sci ; 106(9): 6353-6364, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37479579

RESUMO

During the first 3 wk of life, the immune system of newborn ruminants starts to work, as indicated by fluctuations in the concentrations of proinflammatory cytokines and acute phase proteins (APP). They have been shown to be markers for short and long-term weight gain in ruminants. This observational study investigated these proteins as possible indicators of first lactation performance of dairy cows. A total of 117 dairy calves from a single farm were enrolled in the study. Serum and fecal samples were taken once a week for the first 3 wk of life. Cryptosporidium spp. infection and its treatment were monitored and accounted for in statistical analysis. The concentrations of the APP serum amyloid A (SAA) and haptoglobin (Hp), and the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed in serum. After the first lactation, health and performance data of the cows were retrieved, and associations between APP and cytokine concentrations with first lactation outcomes were investigated through linear and logistic regression. This study found a negative association between the concentration of Hp in the second week of life and average daily weight gain at one year. The SAA concentration measured during the second and third weeks of life was positively associated with age at first calving. IL-6, SAA, and Hp measured in the second week of life were positively associated with calving to conception interval. The concentrations of IL-6 and TNF-α during the first week of life were associated with higher odds of reproductive issues during the first lactation period. These markers can be used to help understand underlying processes that influence animal health and production. In conclusion, inflammatory responses during the first week of life are related to reproductive success, whereas the second and third weeks of life seem to influence the future productive performance in dairy cows.


Assuntos
Doenças dos Bovinos , Criptosporidiose , Cryptosporidium , Feminino , Animais , Bovinos , Interleucina-6 , Reação de Fase Aguda/veterinária , Fator de Necrose Tumoral alfa , Citocinas , Proteínas de Fase Aguda , Haptoglobinas , Lactação , Proteína Amiloide A Sérica
12.
Am J Physiol Renal Physiol ; 325(3): F328-F344, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471421

RESUMO

Prerenal azotemia (PRA) is a major cause of acute kidney injury and uncommonly studied in preclinical models. We sought to develop and characterize a novel model of PRA that meets the clinical definition: acute loss of glomerular filtration rate (GFR) that returns to baseline with resuscitation. Adult male C57BL/6J wild-type (WT) and IL-6-/- mice were studied. Intraperitoneal furosemide (4 mg) or vehicle was administered at time = 0 and 3 h to induce PRA from volume loss. Resuscitation began at 6 h with 1 mL intraperitoneal saline for four times for 36 h. Six hours after furosemide administration, measured glomerular filtration rate was 25% of baseline and returned to baseline after saline resuscitation at 48 h. After 6 h of PRA, plasma interleukin (IL)-6 was significantly increased, kidney and liver histology were normal, kidney and liver lactate were normal, and kidney injury molecule-1 immunofluorescence was negative. There were 327 differentially regulated genes upregulated in the liver, and the acute phase response was the most significantly upregulated pathway; 84 of the upregulated genes (25%) were suppressed in IL-6-/- mice, and the acute phase response was the most significantly suppressed pathway. Significantly upregulated genes and their proteins were also investigated and included serum amyloid A2, serum amyloid A1, lipocalin 2, chemokine (C-X-C motif) ligand 1, and haptoglobin; hepatic gene expression and plasma protein levels were all increased in wild-type PRA and were all reduced in IL-6-/- PRA. This work demonstrates previously unknown systemic effects of PRA that includes IL-6-mediated upregulation of the hepatic acute phase response.NEW & NOTEWORTHY Prerenal azotemia (PRA) accounts for a third of acute kidney injury (AKI) cases yet is rarely studied in preclinical models. We developed a clinically defined murine model of prerenal azotemia characterized by a 75% decrease in measured glomerular filtration rate (GFR), return of measured glomerular filtration rate to baseline with resuscitation, and absent tubular injury. Numerous systemic effects were observed, such as increased plasma interleukin-6 (IL-6) and upregulation of the hepatic acute phase response.


Assuntos
Injúria Renal Aguda , Azotemia , Animais , Masculino , Camundongos , Injúria Renal Aguda/metabolismo , Reação de Fase Aguda/complicações , Azotemia/complicações , Biomarcadores , Modelos Animais de Doenças , Furosemida , Taxa de Filtração Glomerular/fisiologia , Interleucina-6/genética , Interleucina-6/metabolismo , Lipocalina-2/genética , Fígado/metabolismo , Camundongos Endogâmicos C57BL
13.
Basic Clin Pharmacol Toxicol ; 133(3): 265-278, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37312155

RESUMO

Inhalation studies are the gold standard for assessing the toxicity of airborne materials. They require considerable time, special equipment, and large amounts of test material. Intratracheal instillation is considered a screening and hazard assessment tool as it is simple, quick, allows control of the applied dose, and requires less test material. The particle-induced pulmonary inflammation and acute phase response in mice caused by intratracheal instillation or inhalation of molybdenum disulphide or tungsten particles were compared. End points included neutrophil numbers in bronchoalveolar lavage fluid, Saa3 mRNA levels in lung tissue and Saa1 mRNA levels in liver tissue, and SAA3 plasma protein. Acute phase response was used as a biomarker for the risk of cardiovascular disease. Intratracheal instillation of molybdenum disulphide or tungsten particles did not produce pulmonary inflammation, while molybdenum disulphide particles induced pulmonary acute phase response with both exposure methods and systemic acute phase response after intratracheal instillation. Inhalation and intratracheal instillation showed similar dose-response relationships for pulmonary and systemic acute phase response when molybdenum disulphide was expressed as dosed surface area. Both exposure methods showed similar responses for molybdenum disulphide and tungsten, suggesting that intratracheal instillation can be used for screening particle-induced acute phase response and thereby particle-induced cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Tungstênio , Animais , Camundongos , Reação de Fase Aguda/induzido quimicamente , RNA Mensageiro
14.
Osteoporos Int ; 34(9): 1653-1655, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37322374

RESUMO

Although anemia, thrombocytopenia, and mild lymphopenia have been reported in the acute phase response after zoledronic acid, severe lymphopenia has not been reported. This article describes a case of severe lymphopenia following a 5 mg zoledronic acid infusion administered to treat osteoporosis. Zoledronic acid is used to treat osteoporosis, hypercalcemia, Paget's disease, and solid malignancies, including multiple myeloma, breast cancer, and prostate cancer. An acute phase response can be seen in 42% of patients after zoledronic acid treatment. Acute phase response may be accompanied by short-term spontaneously recovered anemia, thrombocytopenia, and severe lymphopenia.


Assuntos
Anemia , Conservadores da Densidade Óssea , Linfopenia , Osteoporose , Trombocitopenia , Masculino , Humanos , Ácido Zoledrônico/efeitos adversos , Difosfonatos , Reação de Fase Aguda/induzido quimicamente , Imidazóis , Infusões Intravenosas , Osteoporose/tratamento farmacológico , Osteoporose/induzido quimicamente , Trombocitopenia/induzido quimicamente , Linfopenia/induzido quimicamente , Anemia/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos
15.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37140541

RESUMO

Arginine (ARG) and Glutamine (GLN) have been reported to play significant roles in protein metabolism, immunity, and intestinal health in weanling pigs. The present study investigated the independent and interactive effect of supplementing ARG and GLN on pigs immune status and growth performance following an Escherichia coli F4 challenge. A total of 240 mixed-sex pigs (24 ±â€…2 d old; 7.3 ±â€…0.1 kg BW) were used in a 42-d experiment after selection for E. coli F4 susceptibility. The pigs were group-housed (3 pigs per pen), and pens were randomly assigned to five experimental treatments (N = 16 pens per treatment). Experimental treatments were: 1) a wheat-barley-soybean meal-based basal diet (CTRL), 2) a basal diet with 2500 mg/kg zinc oxide (ZnO), 3) a basal diet + 0.5% Glutamine (0.5% GLN), 4) basal diet + 0.5% Arginine (0.5% ARG), and 5) basal diet with 0.5% Glutamine + 0.5% Arginine (0.5% GLN + ARG). All Pigs were inoculated with E. coli F4 on days 7, 8, and 9 post-weaning. Rectal swabs were taken from each pig and plated on blood agar plates for E. coli F4 presence. Blood and fecal samples were taken to determine the acute phase response and selected fecal biomarkers for the immune response. Growth performance and fecal scores were recorded. Fecal swabs resulted in no positive pig for E. coli F4 before inoculation and 73.3% positive postinoculation. Diarrhea incidence during days 7 to 14 was significantly lower for the ZnO treatment (P < 0.05). The haptoglobin level on day 3 was lower than days 10 and 20, irrespective of treatment (P < 0.05). The albumin level was lower on day 20 compared to days 3 and 10 (P < 0.05). There was no treatment effect on albumin levels regardless of sampling day (P > 0.05). The PigMAP was lowest on day 3 and highest on day 10 (P < 0.05). We did not observe significant treatment differences (P > 0.05) in myeloperoxidase and calprotectin. Pancreatitis-associated protein was higher in the ZnO (P = 0.001) treatment than in the other treatments. Fecal IgA tended (P = 0.10) to be higher in the ZnO and 0.5% ARG treatments. There were no performance differences, except during days 0 to 7, where the ZnO treatment was lower in average daily gain and average daily feed intake (P < 0.001), while feed efficiency (G:F) FE was similar across treatments. In summary, no improved performance was observed with either ARG, glutamate, or both. The immune response results showed that the E. coli F4 challenge may have exacerbated the acute phase response; hence, the benefits of dietary treatments did not go beyond immune repair and reduction in inflammation.


The supplementation of functional amino acids such as arginine and glutamine has been reported to improve growth performance in weanling pigs. However, during periods of enteric Escherichia coli challenge, results have been inconsistent. Here, we investigated whether independent or combined arginine and glutamine supplementation could improve performance and immune response under an E. coli F4 challenge. The results showed no performance improvements but an improvement in the acute phase response and immune response status. Thus, the benefit of supplemental arginine and glutamine may be prioritized towards building an immune response rather than growth under conditions of an enteric immune challenge.


Assuntos
Doenças dos Suínos , Óxido de Zinco , Suínos , Animais , Escherichia coli , Glutamina/farmacologia , Óxido de Zinco/farmacologia , Reação de Fase Aguda/veterinária , Dieta/veterinária , Suplementos Nutricionais , Arginina/farmacologia , Albuminas , Ração Animal/análise , Desmame
16.
J Vet Intern Med ; 37(3): 925-935, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37186013

RESUMO

BACKGROUND: Chronic enteropathy (CE) is common in dogs and can occur with multiple etiologies including food-responsive enteropathy (FRE) and idiopathic inflammatory bowel disease (IBD). HYPOTHESIS/OBJECTIVE: To study the protein profile and pathway differences among dogs with FRE, IBD, and healthy controls using serum proteome analysis. ANIMALS: Nine CE dogs with signs of gastrointestinal disease and histologically confirmed chronic inflammatory enteropathy and 16 healthy controls. METHODS: A cross-sectional study with cases recruited from 2 veterinary hospitals between May 2019 and November 2020 was performed. Serum samples were analyzed using mass spectrometry-based proteomic techniques. RESULTS: Proteomic profiles showed marked variation in relative protein abundances. Forty-five proteins were significantly (P ≤ .01) differentially expressed among the dogs with CE and controls with ≥2-fold change in abundance. The fold change of dogs with IBD normalized to controls was more pronounced for the majority of proteins than that seen in the dogs with FRE normalized to control dogs. Proteins involving reactive oxygen species, cytokine activation, acute phase response signaling, and lipid metabolism were altered in dogs with CE. CONCLUSIONS AND CLINICAL IMPORTANCE: Cytokine alterations, acute phase response signaling, and lipid metabolism are likely involved in pathogenesis of CE. Although there are insufficient current data to justify the use of proteomic biomarkers for assessment of CE in dogs, our study identifies potential candidates.


Assuntos
Doenças do Cão , Doenças Inflamatórias Intestinais , Cães , Animais , Proteoma , Reação de Fase Aguda/veterinária , Estudos Transversais , Proteômica , Doenças Inflamatórias Intestinais/veterinária , Doenças Inflamatórias Intestinais/metabolismo , Citocinas , Doenças do Cão/diagnóstico
17.
Osteoporos Int ; 34(9): 1613-1623, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37247006

RESUMO

This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not. INTRODUCTION: Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery. METHODS: This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account. RESULTS: In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio [HR] 1.97 (95% CI, 1.09-3.56; P-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11-0.70; P-value = 0.007). CONCLUSIONS: Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.


Assuntos
Conservadores da Densidade Óssea , Fraturas por Osteoporose , Idoso , Humanos , Pessoa de Meia-Idade , Reação de Fase Aguda/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos , Fraturas por Osteoporose/epidemiologia , Estudos Retrospectivos , Ácido Zoledrônico/efeitos adversos
18.
Thromb Haemost ; 123(9): 867-879, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37037212

RESUMO

To identify recurrent inflammation in hemophilia, we assessed the acute-phase response in the blood of patients with hemophilia A and B. Compared to age- and weight-matched controls, blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and LPS-binding protein (LBP) were significantly elevated in the entire cohort of hemophilia patients but exhibited a particularly pronounced increase in obese hemophilia patients with a body mass index (BMI) ≥30. Subgroup analysis of the remaining nonobese hemophilia patients (BMI: 18-29.9) revealed a significant spike of IL-6, CRP, and LBP in connection with a de-novo increase of soluble IL-6 receptor α (sIL-6Rα) in patients with bleeding events within the last month. Hemophilia patients who did not experience recent bleeding had IL-6, CRP, and sIL-6Rα blood levels similar to healthy controls. We did not find increased IL-6 or acute-phase reactants in hemophilia patients with arthropathy or infectious disease. The role of IL-6 as a marker of bleeding in hemophilia was confirmed in hemophilia patients with acute bleeding events as well as in transgenic hemophilia mice after needle puncture of the knee, which exhibited an extensive hematoma and a 150-fold increase of IL-6 blood levels within 7 days of the injury compared to needle-punctured control mice. Notably, IL-6 blood levels shrunk to a fourfold elevation in hemophilia mice over controls after 28 days, when the hematoma was replaced by arthrofibrosis. These findings indicate that acute-phase reactants in combination with sIL-6Rα could be sensitive biomarkers for the detection of acute and recent bleeding events in hemophilia.


Assuntos
Hemofilia A , Camundongos , Animais , Hemofilia A/diagnóstico , Interleucina-6/metabolismo , Reação de Fase Aguda , Proteína C-Reativa/metabolismo , Camundongos Transgênicos , Hematoma
19.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37115605

RESUMO

The objective was to provide an updated profile of the bovine acute-phase response to include recent advancements in technologies and expanded hematological, cytokine, and serum chemistry variables. Beef steers (n = 32; body weight [BW] = 251 ±â€…19.5 kg) were fitted with indwelling jugular catheters 1 d before lipopolysaccharide (LPS; 0.25 µg LPS/kg BW from Escherichia coli O111:B4) administration to facilitate serial blood collection. Rectal temperature was measured using indwelling probes, and ocular temperature was measured using infrared thermal imaging. Blood samples were collected for subsequent analysis of serum chemistry, hematology, and cytokine concentrations. Pearson correlation of rectal temperature and ocular infrared temperature was 0.61 (P < 0.01) and the Spearman correlation coefficient was 0.56 (P < 0.01). Interactions of hour × method were observed for ocular and rectal measurements of body temperature in response to endotoxin exposure. Maximum observed temperature was 39.6 °C at 2.5 h for both rectal and ocular measurements. Body temperature differed by method at hours 0.5, 2.5, 4.5, 7.5, 12.5, 36.5, and 47.5 (P < 0.01), but were not different otherwise. All variables of serum chemistry and complete blood count were influenced by LPS administration, except creatinine, serum glucose, and percent basophils (P ≤ 0.02). Alanine aminotransferase and alkaline phosphatase peaked at hour 2 relative to LPS administration, returned to baseline at hour 12 and continued to decrease below the baseline value at hour 48 (P < 0.01). Total protein concentration decreased 3% in response to LPS (P = 0.01). Total white blood cell count decreased 75% after LPS administration at hour 1 (P < 0.01). Lymphocyte count recovered to baseline at hour 6; sooner than neutrophil count at hour 36. Serum cortisol concentration increased 294% relative to baseline at hour 1 followed by a sustained decrease and return to normal concentration at hour 4 (P < 0.01). Additionally, circulating cytokine concentrations changed with time in response to the LPS challenge, excluding aFGF, bFGF, IGF-1, IL-2, IL-4, MCP-1, and ANG-1 (P ≤ 0.08). Maximum observed concentration of TNF-α at hour 1 was 117% greater than the pre-challenge value (P < 0.01). Data presented herein add to existing works to understand the endocrine and immune responses of beef steers administered exogenous LPS, and incorporate recent technologies, additional biomarkers, and an expanded cytokine profile that can be used as referential data in future research.


The acute phase response is a component of innate immunity initiated by infection, inflammation, or tissue damage. Characteristics of these host responses can be emulated by administration of exogenous endotoxin and closely studied in controlled settings to understand the response to inflammatory diseases that are commonplace in livestock production. Beef steers were administered exogenous lipopolysaccharide, and responses of body temperature, serum chemistry, complete blood count, cortisol, and cytokines were quantified. A moderate correlation of body temperature measured via rectal probe or ocular infrared temperature was observed, but both methods had a similar temporal response and were sensitive to changes in body temperature. Response of serum chemistry variables highlighted the links between metabolism and the inflammatory response. The initial inflammatory response was initiated by cortisol and pro-inflammatory cytokines at hour 1 and tempered by anti-inflammatory cytokines at hours 3 and 4. Therefore, these data offer an expanded view to our understanding of the bovine acute phase response.


Assuntos
Reação de Fase Aguda , Doenças dos Bovinos , Bovinos , Animais , Reação de Fase Aguda/veterinária , Lipopolissacarídeos/farmacologia , Citocinas/metabolismo , Hidrocortisona , Temperatura
20.
J Equine Vet Sci ; 126: 104497, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37088110

RESUMO

Fibrinogen and serum amyloid A (SAA) are commonly measured equine acute phase proteins. Limited data exist on SAA and fibrinogen responses to combination vaccination protocols in horses. A prospective cohort study evaluating SAA, fibrinogen, and rectal temperature following a standard combination vaccination. Blood for measurement of SAA and serum fibrinogen and rectal temperatures were obtained before (0 hour) and after vaccination (24, 48, 72, 96, 168 hours). After vaccination, SAA and fibrinogen increased in all horses. Imports had elevated SAA from 24-168 hours, whereas native horses returned to baseline by 168 hours. Compared to native horses, SAA was significantly higher in imports (coefficient 24-168 hours 358, 95%CI: 46-671 mg/L; P = .03). Fibrinogen increased significantly from 24 to 168 hours postvaccination, but groups did not differ (coefficient -16; 95%CI: -69 to 37 mg/dL; P = .5). Absolute rectal temperatures were significantly higher in imports throughout, including 0 hour (median 37.8; IQR 37.7-38.0 vs. 37.3; 37.1-37.3; P = .002). At 24 hours postvaccination when temperatures significantly increased above baseline in both groups, there was a small but significant difference in the percent change relative to baseline (coefficient 1.9; 95%CI 0.8%-2.9%; P = .002). A standard combination vaccination protocol elicited an acute phase response in all horses. Compared to native previously vaccinated horses, imports had a stronger SAA response. The observed response is worthy of consideration when examining recently vaccinated imported horses.


Assuntos
Proteínas de Fase Aguda , Doenças dos Cavalos , Cavalos , Animais , Reação de Fase Aguda/veterinária , Estudos Prospectivos , Doenças dos Cavalos/metabolismo , Proteína Amiloide A Sérica/análise , Proteína Amiloide A Sérica/metabolismo , Fibrinogênio/metabolismo , Vacinação/veterinária
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