NUTRITIONAL STRESS AND THE ACUTE-PHASE REACTANTS OF RAT SERUM IN EXPERIMENTAL INFLAMMATION

1965 ◽  
Vol 43 (6) ◽  
pp. 925-935 ◽  
Author(s):  
Henry E. Weimer ◽  
James F. Godfrey

The effects of acute starvation, food restriction, and protein depletion on the response of serum proteins to turpentine-induced inflammation were investigated in adult, male, Sprague–Dawley rats. The animals were fed nutritionally inadequate diets until a 20% weight loss was attained, then they were challenged. Significant increases occurred in the concentrations of protein-bound hexose, protein-bound hexosamine, and protein-bound sialic acid, and in the fibrinogen, seromucoid, α2- and β-globulin fractions; a new protein, α2-AP (acute-phase) globulin, appeared in the serum concomitant with decreased levels of total protein, albumin, and γ-globulin after the injection of the phlogogenic agent. The same pattern of response to inflammation occurred, irrespective of whether the rats were fed the stock or experimental diets.The conclusion was drawn that the response of the acute-phase reactants of rat serum to tissue injury is of such magnitude that it is not suppressed by several types of severe nutritional stress. Possible factors involved in the response are discussed.

1967 ◽  
Vol 45 (12) ◽  
pp. 1937-1941 ◽  
Author(s):  
Henry E. Weimer ◽  
Constance Humelbaugh ◽  
Dorothy M. Roberts

The effects of growth of the Walker 256 carcinosarcoma on the α2-AP (acute phase) globulin, fibrinogen, seromucoid, and haptoglobin fractions of plasma were investigated in adult, male Sprague–Dawley rats in a longitudinal study. Early increases in α2-AP globulin and seromucoid levels were found to be related to the tissue injury associated with the implantation procedure. Significant elevations in the α2-AP globulin, fibrinogen, and seromucoid fractions coincided with the onset of progressive tumor growth. Serum haptoglobin concentrations exhibited a delayed rise. This was attributed to the in vivo formation of haptoglobin–hemoglobin complexes. It was suggested that the increases in all fractions reflected the release of humoral mediators from injured or necrotic cells wrhich stimulated increased synthesis of the fractions by the liver.


1967 ◽  
Vol 45 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Henry E. Weimer ◽  
Constance Humelbaugh

The effects of periodic challenge with turpentine on the concentration of the acute-phase reactants of serum were studied in young, adult, male Sprague–Dawley rats. The initial injection of the phlogogenic agent was followed by rapid and significant increases in the concentrations of plasma fibrinogen, total serum glycoprotein, serum complement, and the α2-AP globulin and seromucoid fractions. Variable response patterns were observed on subsequent challenges and in the intervals between. The conclusion was drawn that the acute-phase reactants of serum do not respond in a uniform manner to repeated challenge with a phlogogenic agent, and by inference their synthesis must be regulated by several different mechanisms.


Author(s):  
Sheon Mary ◽  
Heather Small ◽  
Florian Herse ◽  
Emma Carrick ◽  
Arun Flynn ◽  
...  

Pre-existing or new onset of hypertension affects pregnancy and is one of the leading causes of maternal and fetal morbidity and mortality. In certain cases, it also leads to long term maternal cardiovascular complications. The placenta is a key player in the pathogenesis of complicated hypertensive pregnancies, however the pathomechanisms leading to an abnormal placenta are poorly understood. In this study we compared the placental proteome of two rat models: a pre-existing hypertension pregnancy model (stroke-prone spontaneously hypertensive, SHRSP) and the transgenic RAS activated gestational hypertension model (transgenic for human angiotensinogen Sprague-Dawley rats, SD-PE). Label-free proteomics using nano LC-MS/MS was performed for identification and quantification of proteins. Between the two models, we found widespread differences in the expression of placental proteins including those related to hypertension, inflammation and trophoblast invasion; whereas pathways such as regulation of serine endopeptidase activity, tissue injury response, coagulation and complement activation were enriched in both models. We present for the first time the placental proteome of SHRSP and SD-PE and provide insight into the molecular make-up of models of hypertensive pregnancy. Our study informs future research into specific preeclampsia and chronic hypertension pregnancy mechanisms and translation of rodent data to the clinic.


2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Laura Chimenti ◽  
Luis Morales-Quinteros ◽  
Ferranda Puig ◽  
Marta Camprubi-Rimblas ◽  
Raquel Guillamat-Prats ◽  
...  

Abstract Background The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. Aim To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Materials and methods Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. Results At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Conclusions Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI.


2021 ◽  
Vol 15 ◽  
Author(s):  
Han Qiu ◽  
Tianyang Qian ◽  
Tong Wu ◽  
Ting Gao ◽  
Qinghe Xing ◽  
...  

Hypoxic-ischemic (HI) injury is one of the initial factors contributing to neonatal brain injury. Src family kinases (SFKs) are considered to act as molecular hubs for N-methyl-d-aspartate receptor (NMDAR) regulation and participate in the HI injury process. The objectives of this study were to evaluate the levels of phospho-Src (p-Src), the relationship between NMDARs and SFKs, and the effects of SFK inhibition on an immature rat HI brain injury model. The model was induced in 3-day-old Sprague–Dawley rats using the Rice-Vannucci model operation. The level of p-Src was evaluated using Western blotting. The association of NMDARs with SFKs was detected using Western blotting and coimmunoprecipitation. After intraperitoneal injection of 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2), an SFK-selective inhibitor, neuropathological changes were observed by performing H&E and immunofluorescence staining, and the neurological functions were assessed using the following behavioral tests: modified neurological severity score, open field test, and Morris water maze test. The levels of p-Src first decreased at 0 h after injury, increased at 2 h after injury, and continuously decreased from 6 h to 3 days. Along with the increased p-Src levels observed at 2 h after injury, the phosphorylation of NMDAR subunit NR2B at tyrosine 1472 was increased. Following the administration of PP2, the increased p-Src and NMDAR-2B levels detected at 2 h after injury were decreased, and tissue injury and myelin basic protein expression were improved at 7 days after injury. The PP2 intervention improved the performance of injured rats on behavioral tests. In conclusion, we determined the patterns of p-Src expression after HI brain injury in immature rats and showed a relationship with the activated NMDA receptor. The inhibition of p-Src ameliorates neuropathological changes and damages neurological functions induced by HI injury.


1988 ◽  
Vol 34 (10) ◽  
pp. 1992-1994 ◽  
Author(s):  
R G Reed ◽  
L K Davidson ◽  
C M Burrington ◽  
T Peters

Abstract In hepatobiliary disease and biliary obstruction, bilirubin often becomes covalently bound to albumin circulating in serum, producing a nondissociable complex. To determine how long this complexed bilirubin remains in the circulation, we compared the metabolic clearance of bilirubin-albumin complexes with the clearances of free bilirubin and unmodified albumin. Radiolabeled bilirubin, albumin, and covalent bilirubin-albumin were injected into the circulation of Sprague-Dawley rats and serial samples of plasma were analyzed for the injected compounds. The half-life of bilirubin was 6.2 min. The half-life of bilirubin covalently bound to rat serum albumin was 1.9 to 2.1 days, identical to that of unmodified rat albumin. We conclude that bilirubin covalently attached to albumin is maintained in the circulation with the long half-life of albumin rather than the short half-life of bilirubin. Because albumin in humans has a half-life of 19 days, covalent attachment of bilirubin to human albumin could result in persistence of hyperbilirubinemia long after the resolution of disease.


1991 ◽  
Vol 261 (3) ◽  
pp. C461-C466 ◽  
Author(s):  
S. J. Schwarzenberg ◽  
C. J. Potter ◽  
S. A. Berry

For evaluation of the ontogenetic regulation of the acute phase response, inflammation was induced in Fischer rat litters at different postnatal ages. Four homologous rat hepatic serine protease inhibitor (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin) mRNAs were measured in livers 24 h after injection. Animals mounted both positive and negative acute phase responses at all ages, but responses were blunted in young animals, reaching adult levels by days 7-19. alpha 1-Antitrypsin mRNA had no response, and Spi 2.2 mRNA had 50% the rise seen in adults on days 3 and 7. Spi 2.1 and 2.3 mRNAs, negative acute phase reactants, showed attenuation of adult response to inflammation in infant animals of 33% (Spi 2.1) and 40% (Spi 2.3). In hypophysectomized animals, the responses of Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs after turpentine stimulation were similar to that of normal animals, whereas Spi 2.1 mRNA did not change. In conclusion, infant animals mount a blunted response to tissue injury; multiple factors may be involved in the development of the full adult response. Immaturity of the pituitary may play a role in the suppression of Spi 2.1 mRNA's response during inflammation in infant animals. These highly evolutionary related genes will be helpful in identifying specific factors regulating gene expression in inflammation and development.


2002 ◽  
Vol 9 (4) ◽  
pp. 852-857
Author(s):  
M. J. Núñez ◽  
J. Balboa ◽  
P. Riveiro ◽  
D. Liñares ◽  
P. Mañá ◽  
...  

ABSTRACT Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans. Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a central benzodiazepine anxiolytic agonist, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Application of stress and treatment with drugs (placebo or alprazolam) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments (day 15 postinoculation). Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that stress exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in stressed rats compared to those found in the unstressed rats. Treatment with alprazolam significantly reversed these adverse effects of stress, showing that, besides the psychopharmacological properties of this anxiolytic drug against stress, it has consequences for Candida infection.


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