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A proper knowledge of biochemical parameters and inflammatory markers like serum amyloid A (SAA) is crucial in the monitoring of the first post-partum period in equids. Since no information is available on SAA for donkeys at this stage, 50 animals including jennies (n.10) and newborn foals (n.10) within 48 hr from foaling, and jennies (n.10) and foals (n.20) after 30 days from parturition were enrolled in the study to assess routine biochemical profile including SAA. Jennies showed higher alkaline phosphatase and lower bilirubins and cholesterol at 30 days of lactation compared to post-partum. Neonatal donkey foals showed significant higher concentrations of sodium, alkaline phosphatase, lactic dehydrogenase, blood urea nitrogen, creatinine and albumin within 48 hr of age, whilst higher values of phosphate and triglycerides were observed in older foals of 30 days of age. Significant higher SAA concentrations were recorded during the peripartum period in both jennies (25.95 ± 14.98 μg/ml) and newborn donkey foals (37.44 ± 19.75 μg/ml) compared to SAA values recorded in lactating jennies (2.38 ± 1.78 μg/ml) and in donkey foals (16.04 ± 18.14 μg/ml) at 30 days after parturition. The assessment of SAA in jennies and donkey foals around parturition and one month after foaling represents a valuable tool for the monitoring of health status during this stage when animals have to face with new challenges like the peak of lactation and extrauterine life adaptation respectively.

BACKGROUND Sepsis is a significant cause of morbidity and mortality in neonatal foals, especially during the first 7 days of life. Diagnosing sepsis in neonatal foals can be challenging because initial clinical signs are often ambiguous and non-specific. OBJECTIVES To determine if the major acute phase protein serum amyloid A (SAA) as measured by a point-of-care SAA testing device can be used as an evidence-based biomarker of sepsis. STUDY DESIGN Retrospective cohort. METHODS Clinical diagnosis of sepsis based on positive bacterial blood culture or a positive sepsis score was obtained and compared to SAA values in a population of neonatal foals on a breeding farm and referral hospital during four consecutive foaling seasons. A rapid, point-of-care blood test was used to measure SAA concentrations in neonatal foals

OBJECTIVE To investigate the, equine inflammatory response to ventral midline celiotomy in the absence of gastrointestinal disease in horses of varying body condition scores primarily using serial measurements of serum amyloid A (SAA). DESIGN Experimental clinical study. SETTING University teaching hospital. ANIMALS Ten adult light breed horses free of any clinical disease, 5 with body condition score (BCS) 3-4/9 and 5 with BCS 7-8/9. INTERVENTIONS Horses had a ventral midline celiotomy performed under general anesthesia, including manual decompression of the small intestine. SAA, semiquantitative fibrinogen, plasma lactate, and WBC count were measured in the blood preoperatively and at 12, 24, 48, 72, 120, and 168 hours postoperatively. Complete serum biochemistry was performed preoperatively and 24 and 72 hours postoperatively. Serial abdominocentesis was also performed with peritoneal fluid analysis of SAA, total protein, lactate, WBC count, and cytology. MEASUREMENTS AND MAIN RESULTS Significant (P

Serum amyloid A (SAA) is an acute-phase protein (APP) to which multiple immunological functions have been attributed. Regardless, the true biological role of SAA remains poorly understood. SAA is remarkably conserved in mammalian evolution, thereby suggesting an important biological function. Since its discovery in the 1970s, the majority of researchers have investigated SAA using recombinant forms made available through bacterial expression. Nevertheless, recent studies indicate that these recombinant forms of SAA are unreliable. Indeed, commercial SAA variants have been shown to be contaminated with bacterial products including lipopolysaccharides and lipoproteins. As such, biological activities and receptor usage (TLR2, TLR4) revealed through the use of commercial SAA variants may not reflect the inherent nature of this APP. Within this review, we discuss the biological effects of SAA that have been demonstrated through more solid experimental approaches. SAA takes part in the innate immune response via the recruitment of leucocytes and executes, through pathogen recognition, antimicrobial activity. Knockout animal models implicate SAA in a range of functions, such as regulation of T-cell-mediated responses and monopoiesis. Moreover, through its structural motifs, not only does SAA function as an extracellular matrix protein, but it also binds extracellular matrix proteins. Finally, we here also provide an overview of definite SAA receptor-mediated functions and highlight those that are yet to be validated. The role of FPR2 in SAA-mediated leucocyte recruitment has been confirmed; nevertheless, SAA has been linked to a range of other receptors including CD36, SR-BI/II, RAGE and P2RX7. ispartof: IMMUNOLOGY vol:163 issue:2 pages:115-127 ispartof: location:England status: published

Serum amyloid A (SAA) is an apo-lipoprotein produced by the liver in response to proinflammatory cytokines. Few data are available on SAA levels in patients with idiopathic pulmonary fibrosis (IPF), the most common idiopathic form of interstitial pneumonitis (ILD). This study compared SAA concentration in IPF patients to other ILD groups to explore its potential use as a clinical biomarker.

This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 ± 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.

Maintenance of homeostasis at body barriers that are constantly challenged by microbes, toxins and potentially bioactive (macro)molecules requires complex, highly orchestrated mechanisms of protection. Recent discoveries in respiratory research have shed light on the unprecedented role of airway epithelial cells (AEC), which, besides immune cells homing to the lung, also significantly contribute to host defence by expressing membrane‐bound and soluble pattern recognition receptors (sPRR). Recent evidence suggests that distinct, evolutionary ancient, sPRR secreted by AEC might become activated by usually innocuous proteins, commonly referred to as allergens. We here provide a systematic overview on sPRR detectable in the mucus lining of AEC. Some of them become actively produced and secreted by AECs (like the pentraxins C‐reactive protein and pentraxin 3; the collectins mannose binding protein and surfactant proteins A and D; H‐ficolin; serum amyloid A; and the complement components C3 and C5). Others are elaborated by innate and adaptive immune cells such as monocytes/macrophages and T cells (like the pentraxins C‐reactive protein and pentraxin 3; L‐ficolin; serum amyloid A; and the complement components C3 and C5). Herein we discuss how sPRRs may contribute to homeostasis but sometimes also to overt disease (e.g. airway hyperreactivity and asthma) at the alveolar–air interface., Airway epithelial cells actively contribute to protection of the respiratory tract, by locally secreting soluble pattern recognition receptors (sPRR). The sPRR play critical roles in the recognition of conserved motifs and are linked to complement activation. This article reviews the current knowledge on the involvement of sPRRs in the pathogenesis of allergic airway diseases.

Background Feline parvovirus (FPV) is a common and potentially lethal infectious agent in cats. Objective To assess the prognostic value of age, neuter status, serum concentrations of serum amyloid A (SAA), haptoglobin, cholesterol and total thyroxine (tT4), and the presence of systemic inflammatory response syndrome (SIRS) in cats with panleukopenia. Animals Client‐owned cats with FPV infection diagnosed by a positive fecal ELISA test, positive PCR on feces or blood or both. Methods Retrospective cohort study. The electronic medical database was searched for cats with FPV infection presented between January 2010 and January 2018. Cats were divided into survivors and nonsurvivors according to their survival status 28 days after hospital admission. The prognostic importance of each variable was investigated univariately and by multivariable Cox's proportional‐hazards regression. Finally, receiver operator characteristic (ROC) curve analysis was used to identify the best cutoff value for discriminating survivors from nonsurvivors for the statistically significant prognostic predictors identified by multivariable analysis. Results Seventy cats were enrolled in the study. Multivariable analysis determined that only serum tT4 concentration at hospital admission was significantly (P = .01) associated with survival. A cutoff value of 0.82 μg/dL was identified by ROC curve analysis for serum tT4 concentration in discriminating survivors from nonsurvivors. Sensitivity at this cutoff was 73.9% and specificity was 82.9% (area under the curve, 0.783; 95% confidence interval, 0.668‐0.873; P

Introduction/objectives C-reactive protein (CRP) is commonly monitored to track the activity of inflammation and has become the gold standard in the management of all inflammatory diseases. Indeed, serum amyloid-A (SAA) have seemed to correlate moderately with CRP, but the discrepancy of CRP and SAA levels has often been reported, especially in rheumatoid arthritis. Then, we examined CRP reflects a real magnitude of inflammation in patients with rheumatic and infectious inflammatory diseases. Method A total of 414 patients with infectious and non-infectious inflammatory diseases were enrolled. At initial visit, each patient underwent a clinical assessment and had also laboratory tests such as SAA and CRP. In each patient, we carried out a longitudinal analysis of CRP and SAA levels. We determined the inter-individual correlation between SAA and CRP and also clarified intra-individual changes of SAA/CRP ratio. Results SAA and CRP levels changed approximately linearly over time within individuals irrespective of rheumatic and infectious inflammatory diseases. However, SAA/CRP ratios differed dramatically between patients (from 0.117 to 50.8, median 5.71). In patients with high SAA/CRP ratio (>8.44), SAA is a better predictor of inflammation than CRP. In contrast, CRP is a better predictor in patients with low ratio ( Conclusion The SAA/CRP ratio differed greatly between individuals, but was constant in intra-individuals. Low CRP levels could be accompanied by SAA levels predicting any degree of inflammation, implying that CRP is not reflecting a real magnitude of inflammation. To evaluate the real magnitude of inflammation, to access the SAA/CRP ratio in advance is essential.

Research over the past century has advanced our understanding of allergic airway disease, revealing its immunological underpinnings and enabling the development of therapeutics to manage disease. Atopic diseases in the lung are mediated primarily by T helper 2(Th2) cells, specific-IgE, and eosinophils, members of a canonical Type 2 immune response. Recent seminal research has provided extraordinary clarity surrounding the cells and molecules that launch the allergic cascade. However, the most upstream sensors which initiateType 2 immunity remain poorly understood.

Amyloid A amyloidosis secondary to chronic inflammation involves systemic organs and tissues, including the gastrointestinal tract. In the present case, massive amyloid deposit caused gastric perforation. IgM co‐deposition in the glomeruli was another finding of note.

The efficacy of anti-interleukin-1 (IL-1) drugs in kidney transplant patients with FMF-AA who developed colchicine resistance has not been clearly demonstrated.Thirty nine kidney transplant recipients with FMF-AA were evaluated. Group 1 consisted of patients who were in remission after transplantation with colchine and Group 2 included those who developed colchicine resistance.The mean follow-up of the patients was 88.5 ± 61.9 months. Following the treatment with IL-1 antagonists; serum Amyloid A (SAA) averages (79.4 ± 35.3 mg/L) as well as the average number of hospitalizations per month due to FMF episodes (1.4 ± 0.5 times/month) decreased significantly (26.6 ± 25.9 mg/L and 0.1 ± 0.3 times/month) (p .001). Rates of death with a functional graft were 30% and 0% in group 1 and 2 (p = .086). Biopsy-proven AA amyloidosis recurrence in the allograft was observed in 11 of 19 (58%) and seven of nine (78%) patients in group 1 and 2, respectively. Interestingly, glomerular amyloid deposition was not present in the vast majority of biopsies. De novo vasculer amyloid deposition was observed during treatment.IL-1 antagonist drug and colchicine combination almost completely prevented acute FMF attacks in kidney transplant patients with colchicine resistance. However, amyloid accumulation did not cease during IL-1 antagonist drug treatment.

BACKGROUND Serum amyloid A (SAA) has been identified to trigger inflammation response, and play a crucial role in chronic inflammatory diseases. However, the regulatory mechanism of SAA still remains unclear during the development of periodontitis METHODS: SAA mRNA and protein expression were detected in healthy and inflammatory gingival tissues using real-time polymerase chain reaction (PCR) and immunohistochemistry. Human recombinant SAA (Apo-SAA), Pam3CSK4 (a Toll-like receptor (TLR) 2 ligand), siRNA-SAA, or TLR2 neutralizing antibody was applied to treat human gingival fibroblasts, respectively, or combined. SAA, TLRs, and inflammatory cytokines interleukin (IL)-6 and IL-8 were analyzed by real-time PCR, western blotting, or enzyme-linked immunosorbent assay. RESULTS SAA expression increased in human inflammatory gingival tissues from patients with periodontitis (P

Background Finding a medical treatment which can combat cell proliferation and relax smooth muscles in canine benign prostatic hyperplasia (BPH) appears to be imperative. Aims This study aimed to evaluate the oxidative stress and inflammatory proteins following the treatment of dogs induced for BPH with an anti-proliferative agent called tadalafil. Materials and methods Twenty-five adult intact male dogs were randomly designated into five groups (n = 5): Control group was not induced for BPH and not treated with tadalafil; dogs induced for BPH by testosterone enanthate and estradiol benzoate and treated with tadalafil (5 mg/day P.O.); dogs which received tadalafil (5 mg/day P.O.); dogs induced for BPH and treated with castration; and dogs induced for BPH. Oxidative stress factors (glutathione peroxidase [GPX], superoxide dismutase [SOD], catalase) and inflammatory proteins (haptoglobin, serum amyloid A [SAA], malondialdehyde [MDA]) were measured in the blood serum for four sequential weeks. Results Glutathione peroxidase and SOD serum levels declined in dogs in the BPH-induced group compared to those in the control group. Those levels diminished in BPH-induced castrated and tadalafil-treated groups. The changes in the GPX and SOD serum concentrations were not significant between the BPH-induced castrated group and BPH-induced tadalafil-treated group. Moreover, MDA concentration increased slightly in groups with BPH and groups which were castrated. Generally, however, there were no significant differences in the MDA serum concentrations between other groups. Haptoglobin and SAA concentrations increased in BPH-castrated group. Also, the differences in haptoglobin and SAA were not significant between the groups. Conclusion Tadalafil could not control oxidative stress and inflammatory mediators which happened during BPH in dogs.

BACKGROUND: Acute‐phase proteins may help assess the nature and severity of lesions and outcome in horses undergoing colic surgery. OBJECTIVES: To compare serum amyloid A and plasma fibrinogen concentrations ([SAA] and [fibrinogen]) in the immediate post‐operative period after exploratory celiotomy and determine their value in assessment of post‐operative complications and survival to discharge. STUDY DESIGN: Observational study. METHODS: This study included horses over 1 year of age undergoing exploratory celiotomy. Surgical procedures, lesions, post‐operative care, complications and survival to discharge were recorded. [SAA] and [fibrinogen] were measured prior to surgery and 5 days post‐operatively. Statistical analyses included Yate's Chi‐square test, linear mixed effects model, Mann–Whitney U test and logistic regression. RESULTS: Of 300 horses, 52.0% developed post‐operative complications and 83.7% survived to discharge, with significantly reduced chance of survival in horses that developed post‐operative complications (P

AIMS Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC). METHODS This was a retrospective multicenter study. A clinicopathological investigation was undertaken to compare 62 cases with SH-HCC features to 31 age- and sex-matched standard HCC cases, including an immunohistochemical study using markers for classification of HCA and diagnosis of HCC. RESULTS The characteristic features of SH-HCC compared with standard HCC include a higher rate of complications of MS, more frequent non-alcoholic fatty liver disease as an underlying liver disease, and HCC development in non-cirrhotic liver. The rate of solitary tumors showed no difference between the two groups, but the median diameter of the main tumor was greater in SH-HCCs (45 mm/20 mm, P = 0.01). The HCCs were mostly moderately differentiated, and the patterns were mainly trabecular in both groups. Positive findings for serum amyloid A and C-reactive proteins, classification markers of inflammatory HCA, were significantly higher in cancerous lesions of SH-HCC cases (50%/13%, P

Decreased circulating 25-hydroxyvitamin D (25(OH)D) and increased inflammatory marker concentrations have been reported separately in canine cancer. Correlations between the two exist in humans, but little work has examined links in dogs. This study aimed to determine plasma 25(OH)D and inflammatory marker concentrations in healthy dogs and dogs with cancer and to assess correlations in each group. Newly diagnosed dogs with B-cell lymphoma (B-cell, n=25), T-cell lymphoma (T-cell, n=9), osteosarcoma (OSA, n=21), and mast cell tumour (MCT, n=26) presenting to a tertiary oncology center, and healthy dogs (n=25), were enrolled. Plasma samples were analyzed for 25(OH)D, C-reactive protein (CRP), haptoglobin (HP), serum amyloid A (SAA), alpha-1-acid glycoprotein (AAG), and 13 chemokines and cytokines. Dogs with B-cell had decreased plasma 25(OH)D (p=0.03), and increased plasma CRP, AAG, HP, KC-like and MCP-1 concentrations (p

Objectives The NLRP3 inflammasome plays a key role in arterial wall inflammation. In this study, we elucidated the role of serum lipoproteins in the regulation of NLRP3 inflammasome activation by serum amyloid A (SAA) and other inflammasome activators. Methods The effect of lipoproteins on the NLRP3 inflammasome activation was studied in primary human macrophages and THP‐1 macrophages. The effect of oxidised low‐density lipoprotein (LDL) was examined in an in vivo mouse model of SAA‐induced peritoneal inflammation. Results Native and oxidised high‐density lipoproteins (HDL3) and LDLs inhibited the interaction of SAA with TLR4. HDL3 and LDL inhibited the secretion of interleukin (IL)‐1β and tumor necrosis factor by reducing their transcription. Oxidised forms of these lipoproteins reduced the secretion of mature IL‐1β also by inhibiting the activation of NLRP3 inflammasome induced by SAA, ATP, nigericin and monosodium urate crystals. Specifically, oxidised LDL was found to inhibit the inflammasome complex formation. No cellular uptake of lipoproteins was required, nor intact lipoprotein particles for the inhibitory effect, as the lipid fraction of oxidised LDL was sufficient. The inhibition of NLRP3 inflammasome activation by oxidised LDL was partially dependent on autophagy. Finally, oxidised LDL inhibited the SAA‐induced peritoneal inflammation and IL‐1β secretion in vivo. Conclusions These findings reveal that both HDL3 and LDL inhibit the proinflammatory activity of SAA and this inhibition is further enhanced by lipoprotein oxidation. Thus, lipoproteins possess major anti‐inflammatory functions that hinder the NLRP3 inflammasome‐activating signals, particularly those exerted by SAA, which has important implications in the pathogenesis of cardiovascular diseases., In this study, we found that both low‐ (LDL) and high‐density lipoproteins (HDL3) hinder the binding of serum amyloid A (SAA) to Toll‐like receptor 4 (TLR4), which prevents SAA from activating the NLRP3 inflammasome. We further observed that native lipoproteins exert their inhibitory action on the level of inflammasome priming, but lipoprotein oxidation blocks also the NLRP3 inflammasome activation by inhibiting the complex assembly and by increasing basal autophagy. In the presence of NLRP3 inflammasome‐activating stimuli, oxidised lipoproteins possess major anti‐inflammatory functions.

Background Serum amyloid A (SAA), interleukin‐6 (IL‐6) and neutrophil‐to‐lymphocyte ratio (NLR) play critical roles in inflammation and are used in clinical laboratories as indicators of inflammation‐related diseases. We aimed to provide potential laboratory basis for auxiliary distinguishing coronavirus disease (COVID‐19) by monitoring above indicators. Methods A total of 84 patients with confirmed COVID‐19 were enrolled in the study. Baseline characteristics and laboratory results were collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to combined detection of SAA and IL‐6 in patients with COVID‐19, and independent risk factors for severity of COVID‐19 were assessed by using binary logistic regression. Results The main clinical symptoms of patients with COVID‐19 were fever (98.8%), fatigue (61.9%), and dry cough (58.3%). SAA, IL‐6, and NLR were significantly higher in patients with COVID‐19 (all P, Comparison of laboratory indicators among patients with COVID‐19

Background Although Clostridioides difficile-associated diseases (CDAD) is considered to be associated with colitis in horses, few studies have been performed with a focus on the characteristics of CDAD in thoroughbred racehorses. Methods Between 2010 and 2018, a test for C. difficile was performed using faecal samples from 137 thoroughbred racehorses with colitis presenting with diarrhoea and fever. The mortality rate, clinical findings, predisposing factors and the selected treatments were investigated in a retrospective manner. Results Twenty-four cases were diagnosed as CDAD and 113 as non-CDAD. The mortality rate was significantly higher in the CDAD group (83 per cent) than that in the non-CDAD group (34 per cent). The levels of serum amyloid A, blood urea nitrogen and packed cell volume at initial presentation were also significantly higher, and those of total protein and albumin were significantly lower in the CDAD group. The development of CDAD was associated with the administration of antimicrobials, surgery and hospitalisation. No significant improvement in mortality was observed for any of the selected treatment in both groups. Conclusion CDAD in thoroughbred racehorses was identified as a high mortality disease with rapid progression of systemic inflammation and deterioration of the circulatory state. Further investigation is required to improve the treatment.

BACKGROUND The XPEN60 CRP&SAA (hereafter XPEN60) is a new automated hematology analyzer that can rapidly detect C-reactive protein (CRP), serum amyloid A (SAA), and blood cell counts (CBC), including the 5-part differential of white blood cells (5-DIFF). The aim of this study was to evaluate the analytical performance of XPEN60. METHODS The analytical performance of XPEN60 was evaluated on the basis of several parameters, including the limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), precision, accuracy, carryover, linearity, clinical reportable range (CRR), and interference test. In addition, method comparisons between CBC and 5-DIFF, CRP, and SAA were performed on several systems. RESULTS Total imprecision and accuracy for all parameters fell within acceptable criteria, and excellent measurements were observed in the dilution linearity (coefficient of determination, R2 > .99). LoBs and LoDs (0 and 0.21 mg/L for CRP, 1.1 and 2.27 mg/L for SAA) satisfy the manufacturer's statement. LoQs were 0.61 and 3.62 mg/L for CRP and SAA, respectively. No significant carryover or interference tests (

Background Insulin, insulin-like growth factor-1 (IGF-1), and inflammation possibly are involved in cats with asymptomatic hypertrophic cardiomyopathy (aHCM). Objectives To evaluate echocardiography, morphology, cardiac and inflammatory markers, insulin and IGF-1 in cats with aHCM. Animals Fifty-one client-owned cats with aHCM. Methods Observational descriptive study. Variables (body weight [BW], body condition score [BCS], echocardiography, and serum concentrations of N-terminal pro-B-type natriuretic peptide [NT-proBNP], ultra-sensitive troponin-I [c-TnI], serum amyloid A [SAA], insulin, glucose and IGF-1) were evaluated for significant increases above echocardiography cutoff values and laboratory reference ranges, associations and effect of left atrial (LA) remodeling and generalized hypertrophy. Results Cats with aHCM had BCS >= 6/9 (P = .01) and insulin (P < .001), NT-proBNP (P = .001) and cTn-I (P < .001) above laboratory reference ranges. Associations were present between NT-proBNP and maximum end-diastolic interventricular septum thickness (IVSd; rho = .32; P = .05), maximum end-diastolic left ventricular free wall thickness;(rho = .41; P = .01), LA/Aorta (rho = .52; P = .001) and LA diameter (LA-max; rho = .32; P = .05); c-TnI and LA/Aorta (rho = .49; P = .003) and LA-max (rho = .28; P = .05); and SAA and number of IVSd regions >= 6 mm thickness (rho = .28; P = .05). Body weight and BCS were associated with IGF-1 (r = 0.44; P = .001), and insulin (rho = .33; P = .02), glucose (rho = .29; P = .04) and IGF-1 (rho = .32; P = .02), respectively. Concentrations of NT-proBNP (P = .02) and c-TnI (P = .01), and SAA (P = .02), were higher in cats with LA remodeling, and generalized hypertrophy, respectively. Conclusions and clinical importance Results suggest potential implications of insulin, IGF-1, and inflammation in cats with aHCM, but it remains to be confirmed whether these findings represent a physiological process or a part of the pathogenesis and development of disease. Royal Canin SAS van Hoek, I (reprint author), Royal Canin SAS, Res & Dev, 650 Ave Petite Camargue, F-30470 Aimargues, France. ingrid.van.hoek@royalcanin.com

Background Serum amyloid A (SAA) has been associated with the development and prognosis of cancer. The purpose of this study was to evaluate the predictive value of integration of pretreatment SAA–EBV DNA (S-D) grade and comparison with the TNM staging system in patients with nasopharyngeal carcinoma (NPC). The S-D grade was calculated based on the cut-off values of serum SAA and EBV DNA copy numbers which were determined by receiver operating characteristic (ROC) curves. We evaluated the prognostic value of pretreatment SAA, EBV DNA and S-D grade on overall survival (OS) of NPC patients. We also evaluated the predictive power of S-D grade with TNM staging system using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results A total of 304 NPC patients were enrolled in this study. Multivariate analysis showed that TNM stage (P = 0.007), SAA (P = 0.013), and EBV DNA (P = 0.033) were independent prognostic factors in NPC. The S-D grade was divided into S-D grade 1, S-D grade 2, and S-D grade 3, which had more predictive accuracy for OS than TNM staging according to all 4 indices. Conclusions We found that the S-D grade could be used as a new tool to predict the OS in NPC patients.

Background Accurate antemortem EPM diagnosis requires evidence of intrathecal antibody production. Some advocate the use of acute phase proteins in addition to serology, which alone results in substantial false positives. Hypothesis/objectives The purpose of this study was to determine if serum C-reactive protein (CRP) or serum amyloid A (SAA) concentrations were elevated in cases of equine protozoal myeloencephalitis (EPM) compared to other neurological diseases. Animals 25 clinical cases of equine neurological disease: EPM (10), cervical vertebral stenotic myelopathy (CVSM) (10), neuroborreliosis (2), equine motor neuron disease (1), degenerative myelopathy (1), and leukoencephalomalacia (1). Methods Serum and CSF CRP and SAA were measured. Selection criteria included neurologic disease, antemortem diagnosis of EPM or CVSM, or postmortem diagnosis of EPM, CVSM, or other neurologic disease, and availability of serological results and archived samples for testing. Results Serum SAA and serum CRP levels were generally undetectable or low in horses with EPM (median CRP ≤0.1 mg/L, ≤0.1-14.4 mg/L; median SAA ≤0.1 mg/L, ≤0.1-6.11 mg/L) and CVSM (median CRP ≤0.1, ≤0.1-2.41 mg/L; median SAA ≤0.1mg/L, ≤0.1-13.88 mg/L). CSF CRP and SAA for horses with EPM (median CRP 3.35 mg/l, 0.19-13.43 mg/l; median SAA ≤0.1 mg/L, ≤0.1-2.4 mg/L) and CVSM (median CRP 4.015 mg/L, 0.16-9.62 mg/L; median SAA 0.62 mg/L, ≤0.1-2.91 mg/L) were also undetectable or low. Kruskal-Wallis test showed no statistically significant differences between serum CRP (P = .14), serum SAA (P = .79), spinal fluid CRP (P = .65), or spinal fluid SAA between horses with EPM and CVSM (P = .52). Conclusion Neither SAA nor CRP in serum or CSF aid diagnosis of EPM.

Introduction Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. Methods Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline. Results Mean age was 70 years, mean Mini–Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline ( P = .015). Cerebrospinal fluid intercellular adhesion molecule-1, vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95 for BBB impairment, and serum IL-16, VEGF-D, IL-15, and other variables generated an AUC of 0.92 for BBB impairment. Discussion BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated.

BACKGROUND: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. AIM: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. METHODS: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. RESULTS: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. CONCLUSIONS: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.

The Glasgow Coma Scale (GCS), which classifies patients into mild, moderate or severe traumatic brain injury (TBI), is a system used to prioritize treatment and prognosticate the severity of head injury. In this study, sera of patients with various stages of TBI, as well as control subjects, were analyzed to screen for proteins that may be used to complement the GCS system. By subjecting pooled serum samples to iTRAQ analysis for quantitative comparison of protein abundance, and attesting their altered levels using ELISA, we have detected increased levels of serum amyloid A, C-reactive protein, leucine-rich alpha-2-glycoprotein, lipopolysaccharide-binding protein, fibronectin, vitronectin and alpha-1-antichymotrypsin in patients across all strata of TBI relative to the controls. However, kininogen was decreased only in moderate and severe TBI, whereas apolipoprotein E and zinc-alpha-2-glycoprotein were only increased in severe TBI. Hence, we propose a panel of serum biomarkers, which if analyzed within 24 h of the injury, can be used to diagnose patients with TBI into mild, moderate or severe stratification objectively, thus complementing the traditional GCS.

Background Intellectual disability (ID) is part of the Down syndrome (DS) phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals with DS is not yet fully understood, with many research hypotheses still unproven. Basing on previous studies (which suggested a possible role of altered inflammatory response in DS-related ID), we assessed the serum levels of a number of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP), high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy controls. Methods In total, 24 children diagnosed with DS and 12 healthy controls were enrolled, and all underwent detailed cognitive assessment. Also, serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and correlated to the severity of ID in the DS group. Results Serum SAA, C-RP and HMGB1 values were found to be significantly higher in the DS group compared with the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively correlated with C-RP and SAA in the DS group but not in the healthy controls. Only serum C-RP levels resulted inversely correlated (P 0.05). Conclusions The levels of the determined markers were higher in DS individuals compared with (cognitively) healthy subjects, and CRP showed a negative correlation with IQ in children with DS.

Several epidemiological studies reported an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and atherosclerotic cardiovascular disease (ASCVD). However, therapeutic interventions targeted at raising HDL-cholesterol failed to improve cardiovascular outcomes, suggesting that HDL components distinct from cholesterol may account for the anti-atherothrombotic effects attributed to this lipoprotein. Sphingosine-1-phosphate (S1P) and the acute phase protein serum amyloid A (SAA) have been identified as integral constituents of HDL particles. Evidence suggests that S1P and SAA levels within HDL particles may be affected by inflammation and oxidative stress, which are coexisting processes underlying ASCVD. Because SAA, an inflammation-related marker, and S1P, an anti-atherothrombotic marker, have relatively clear opposite characteristics among the HDL-associated proteins, the approach of assessing the two markers simultaneously may provide new insights in clinical practice (S1P/SAA Index). This review focuses on evidence in support of the concept that the S1P/SAA Index may affect the HDL atheroprotective properties and may, therefore represent a potential target for therapeutic interventions.

Bullous amyloidosis is a rare disease in humans that has not been described in a veterinary species in the peer-reviewed literature. The human disease is characterised by haemorrhagic vesicles and bullae on the skin and mucosae, which form due to amyloid deposition.To describe the clinical features, laboratory analysis and histopathological features of an unique presentation of bullous disease in a horse.A 17-year-old thoroughbred mare presented for weight loss and severe oral cavity ulcers.Investigations involved haematological evaluation, chemistry profiles, gastroscopy and serum protein electrophoresis, and, postmortem, histopathological evaluation, Congo-red staining and transmission electron microscopy (TEM).Haemorrhagic vesicles and bullae occurred on the mucosa of the oral cavity, lips, oesophagus and stomach, and much less the muzzle, face and mucocutaneous areas of the perineum, where scarring was evident. Histopathological evaluation and Congo-red staining confirmed the presence of amyloid deposits in dermis and submucosa, in association with vesicle and bulla formation, consistent with bullous amyloidosis. TEM confirmed amyloid fibril deposition in the dermis and along the basement membrane zone. Clefts occurred in the superficial dermis and submucosa, which explained haemorrhage and scarring. The presence of a polyclonal gammopathy and the rapid abolishment of Congo-red staining with performate pretreatment supported serum amyloid A and secondary amyloidosis.Bullous amyloidosis is a novel disease of the horse and a newly recognised differential for bullous disease, for which the haemorrhagic nature of bullae, scarring and deep secondary ulcers are considered clinical clues to the condition.L’amyloïdose bulleuse est une maladie rare chez l’homme qui n’a pas encore été décrite dans une espèce vétérinaire dans la littérature avec comité de lecture. La maladie de l’homme est caractérisée par des vésicules et bulles hémorragiques de la peau et des muqueuses qui se forment après dépôt d’amyloïde. HYPOTHÈSES/OBJECTIFS: Décrire les données cliniques, les analyses de laboratoires et les critères histopathologiques d’une présentation unique de maladie bulleuse chez un cheval.Une jument de race de 17 ans présentée pour perte de poids et ulcères sévères de la cavité buccale. MÉTHODES: Les investigations comprenaient une évaluation hématologique, des profils biochimiques, une gastroscopie et une électrophorèse des protéines sériques et, post mortem, un examen histopathologique, une coloration au rouge Congo et une microscopie à transmission électronique (TEM). RÉSULTATS: Les vésicules et bulles hémorragiques se sont développées sur les muqueuses de la cavité orale, les lèvres, l’œsophage et l’estomac et moins au niveau des narines, de la face et des jonctions cutanéo-muqueuses du périnée où des cicatrices étaient évidentes. Une évaluation histopathologique et une coloration au rouge Congo ont confirmé la présence d’amyloïde dans le derme et les muqueuses, en association avec la formation des vésicules et des bulles, compatible avec l’amyloïdose bulleuse. La TEM a confirmé le dépôt de fibrilles d’amyloïdes dans le derme et au niveau de la membrane basale. Un clivage était présent dans le derme superficiel et les sous muqueuses, expliquant l’hémorragie et les cicatrices. La présence d’une gammapathie polyconale et du rapide disparition de la coloration au rouge Congo avec réalisation d’un prétraitement, soutenaient une amyloïde A sérique et une amyloïdose secondaire.L’amyloïdose bulleuse est une nouvelle maladie du cheval et un nouveau différentiel dans les dermatoses bulleuses pour laquelle la nature hémorragique des bulles, des cicatrices et des ulcères secondaires profonds est considérée comme une donnée clinique évocatrice de l’atteinte.INTRODUCCIÓN: la amiloidosis bullosa es una enfermedad rara en humanos que no se ha descrito en ninguna especie veterinaria en la literatura revisada. La enfermedad humana se caracteriza por vesículas y ampollas hemorrágicas en la piel y las mucosas, que se forman debido al depósito de amiloide. HIPÓTESIS/OBJETIVOS: describir las características clínicas, análisis de laboratorio y características histopatológicas de una presentación única de enfermedad bullosa en un caballo. ANIMALES: una yegua pura sangre de 17 años que se presentó por pérdida de peso y úlceras severas en la cavidad oral. MÉTODOS: Las investigaciones incluyeron evaluación hematológica, perfiles químicos, gastroscopia y electroforesis de proteínas séricas y, post mortem, evaluación histopatológica, tinción con rojo Congo y microscopía electrónica de transmisión (TEM). RESULTADOS: Se observaron vesículas y ampollas hemorrágicas en la mucosa de la cavidad oral, labios, esófago y estómago, y mucho menos en el hocico, la cara y las áreas mucocutáneas del perineo, donde las cicatrices eran evidentes. La evaluación histopatológica y la tinción con rojo Congo confirmaron la presencia de depósitos de amiloide en dermis y submucosa, en asociación con formación de vesículas y ampollas, compatibles con amiloidosis bullosa. TEM confirmó el depósito de fibrillas de amiloide en la dermis y a lo largo de la zona de la membrana basal. Se produjeron hendiduras en la dermis superficial y la submucosa, lo que explica la hemorragia y la cicatrización. La presencia de una gammapatía policlonal y la rápida desaparición de la tinción con rojo Congo con el pretratamiento con permanganato potásico confirmaron amiloide A sérico y la amiloidosis secundaria. CONCLUSIÓN E IMPORTANCIA CLÍNICA: la amiloidosis bullosa es una enfermedad nueva del caballo y un diferencial recientemente reconocido de enfermedades bullosas. La naturaleza hemorrágica de las ampollas, la presencia de cicatrices y de úlceras secundarias profundas se consideran indicios clínicos de esta enfermedad.Die bullöse Amyloidose ist eine seltene Erkrankung beim Menschen, die noch bei keiner tierischen Spezies in Peer-Review Literatur beschrieben wurde. Die Erkrankung ist beim Menschen durch hämorrhagische Bläschen und Blasen auf der Haut und den Schleimhäuten gekennzeichnet, die sich aufgrund von Amyloid Ablagerung bilden.Die Beschreibung der klinischen Merkmale, der Laboranalyse und der histopathologischen Merkmale einer einzigartigen Präsentation einer bullösen Erkrankung bei einem Pferd.Eine 17 Jahre alte Vollblutaraberstute wurde wegen Gewichtsverlust und hochgradigen Ulzera in der Mundhöhle vorgestellt.Die Untersuchungen beinhalteten Hämatologie, Biochemie, Gastroskopie und eine Serumelektrophorese, sowie post mortem eine histopathologische Evaluierung, Kongorotfärbung und Transmissionselektronenmikroskopie (TEM).Hämorrhagische Bläschen und Blasen traten an der Mundschleimhaut, an den Lippen, der Speiseröhre und im Magen auf, sowie etwas weniger ausgeprägt an der Nase, dem Gesicht und den mucokutanen Übergängen des Perneums, wo Narbenbildung evident war. Die histopathologische Evaluierung und die Kongorotfärbung bestätigten das Vorkommen von Amyloidablagerungen in der Dermis und Submukosa, im Zusammenhang mit Bläschen- und Blasenbildung, was mit einer bullösen Amyloidose übereinstimmte. Die TEM bestätigte Amyloidfasernablagerungen in der Dermis und entlang der Basalmembranzone. In der oberflächlichen Dermis und Submukosa bestand eine Spaltenbildung, die die Blutung und die Narbenbildung erklärten. Das Auftreten eine polyklonalen Gammopathie sowie das rasche Verschwinden der Kongorotfärbung nach performativer Vorbehandlung stützte die Diagnose einer Serum Amyloid A und einer sekundären Amyloidose.Die bullöse Amyloidose ist eine neue Erkrankung des Pferdes und eine neu erkannte Differentialdiagnose für bullöse Erkrankungen, bei der die hämorrhagische Natur der Blasen, die Narbenbildung und die tiefen sekundären Ulzera als klinische Hinweise für diesen Zustand gelten.背景: 水疱性アミロイドーシスは、ヒトではまれな疾患で、獣医学的にはまだ報告されていない。本疾患は、アミロイド沈着により皮膚や粘膜に形成される出血性の小水疱や水疱が特徴である。 仮説/目的: 本研究の目的は、1頭の馬に認められた水疱疾患のユニークな症状の臨床的特徴、実験室解析および病理組織学的特徴を説明することであった。 供試動物: 17歳のサラブレッドの雌馬が体重減少および重度の口腔内潰瘍のために来院した。 方法: 血液学的評価、化学的プロファイル、胃内視鏡検査、血清タンパク質電気泳動を行い、死後、組織学的評価、コンゴレッド染色、透過型電子顕微鏡 (TEM) を行った。 結果: 出血性小水疱および水疱は口腔、口唇、食道、胃の粘膜に発生し、鼻口部、顔面、会陰粘膜皮膚領域にはほとんど発生せず、瘢痕が認められた。病理組織学的評価およびコンゴレッド染色により、水疱性アミロイドーシスと一致した、小水疱や水疱の形成と関連する真皮および粘膜下層のアミロイド沈着の存在が確認された。TEMでは、真皮および基底膜帯に沿ってアミロイド線維の沈着が確認された。表層の真皮および粘膜下層に裂け目が生じており, 出血および瘢痕化が説明できた。ポリクローナルガンモパシーの存在と、前治療の実施によるコンゴレッド染色の急速な廃絶は、血清アミロイド A および続発性アミロイドーシスを支持した。 結論と臨床的重要性: 水疱性アミロイドーシスは馬の新しい病気であり、水疱症の鑑別として新たに認識された。水疱の出血性の性質、瘢痕、深い二次的な潰瘍がこの病気の臨床的な手がかりと考えられる。.背景: 大疱性淀粉样变性是一种人类罕见疾病, 动物发病尚未在兽医同行评审文献中描述过。人类疾病的特征是皮肤和粘膜上的出血性水疱和大疱, 其由淀粉样蛋白沉积形成。 假设/目的: 描述马大疱性疾病独特表现的临床特征、实验室分析和组织病理学特征。 动物: 只17岁的纯种母马因体重减轻和严重的口腔溃疡而就诊。 方法: 研究涉及血液学评价、化学特征、胃镜检查和血清蛋白电泳, 以及尸检、组织病理学评价、刚果红染色和透射电子显微镜(TEM)。 结果: 口腔、嘴唇、食管和胃的粘膜上发生出血性水疱和大疱, 更少发生在有明显瘢痕的口鼻、面部和会阴皮肤粘膜区域。组织病理学评价和刚果红染色证实真皮和粘膜下层存在淀粉样沉积物, 与水泡和大疱形成相关, 与大疱性淀粉样变性一致。TEM证实淀粉样纤维沉积于真皮, 并沿基底膜区沉积。裂隙发生在真皮浅层和粘膜下层, 这解释了出血和瘢痕形成。多克隆丙种球蛋白病的存在和进行预处理后刚果红染色的快速消除,支持了血清淀粉样蛋白a和继发性淀粉样变性。 结论和临床意义: 大疱性淀粉样变性是马的一种新型疾病, 并发现与大疱性疾病存在差异, 大疱的出血性质、瘢痕和深部继发性溃疡被认为是该疾病的临床线索。.A amiloidose bolhosa é uma doença rara em humanos que não foi descrita em espécies veterinárias na literatura com sistema de revisão por pares. A doença humana é caracterizada por vesículas e bolhas hemorrágicas na pele e mucosas, que se formam devido à deposição de substância amiloide. HIPÓTESE/OBJETIVOS: Descrever as características clínicas, exames laboratoriais e histopatológicos de uma doença bolhosa com apresentação singular em um cavalo.Uma égua da raça puro-sangue inglês de 17 anos de idade foi apresentada devido a um quadro de perda de peso e úlceras graves da cavidade oral. MÉTODOS: As investigações consistiram de avaliação hematológica, perfil bioquímico, gastroscopia e eletroforese de proteínas séricas e, postmortem, avaliação histopatológica, coloração com vermelho do Congo e microscopia eletrônica de transmissão (TEM).Vesículas e bolhas hemorrágicas estavam presentes na mucosa da cavidade oral, lábios, esôfago e estômago, e, em menor quantidade, no focinho, face e regiões mucocutâneas do períneo, onde a presença de tecido cicatricial era evidente. A avaliação histopatológica e a coloração com vermelho do Congo confirmaram a presença de depósitos de substância amiloide na derme e submucosa, associados à formação de vesículas e bolhas, compatível com amiloidose bolhosa. A TEM confirmou a deposição de fibrila amiloide na derme e ao longo da zona da membrana basal. Observou-se a presença de fissuras na derme superficial e submucosa, justificando a hemorragia e as cicatrizes. A presença de uma gamopatia policlonal e a rápida descoloração do vermelho do Congo após pré-tratamento corroboraram com a amiloide A sérica e a amiloidose secundária. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: A amiloidose bolhosa é uma nova doença descrita em equinos e representa um diagnóstico diferencial recentemente reconhecido para quadros bolhosos, sendo que a natureza hemorrágica das bolhas, presença de cicatrizes e úlceras profundas secundárias são consideradas indícios clínicos da condição.

Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model.

Accumulating evidence suggests that O3 exposure may contribute to CNS dysfunction. Here, we posit that inflammatory and acute-phase proteins in the circulation increase after O3 exposure and systemically convey signals of O3 exposure to the CNS. To model acute O3 exposure, female Balb/c mice were exposed to 3 ppm O3 or forced air for 2 h and were studied after 6 or 24 h. Of 23 cytokines and chemokines, only KC/CXCL1 was increased in blood 6 h after O3 exposure. The acute-phase protein serum amyloid A (A-SAA) was significantly increased by 24 h, whereas C-reactive protein was unchanged. A-SAA in blood correlated with total leukocytes, macrophages, and neutrophils in bronchoalveolar lavage from O3-exposed mice. A-SAA mRNA and protein were increased in the liver. We found that both isoforms of A-SAA completely crossed the intact blood-brain barrier, although the rate of SAA2.1 influx was approximately 5 times faster than that of SAA1.1. Finally, A-SAA protein, but not mRNA, was increased in the CNS 24 h post-O3 exposure. Our findings suggest that A-SAA is functionally linked to pulmonary inflammation in our O3 exposure model and that A-SAA could be an important systemic signal of O3 exposure to the CNS.-Erickson, M. A., Jude, J., Zhao, H., Rhea, E. M., Salameh, T. S., Jester, W., Pu, S., Harrowitz, J., Nguyen, N., Banks, W. A., Panettieri, R. A., Jr., Jordan-Sciutto, K. L. Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis.

A 3-year-old, spayed female, Domestic Shorthair cat presented with anorexia, lethargy, vomiting, probable hemoabdomen, and multiple masses on the right lateral liver lobe. Clinicopathologic and imaging abnormalities included anemia, azotemia, icterus, and hepatomegaly with hypoechoic masses. On cytologic evaluation of a fine-needle aspiration of a liver mass there was abundant extracellular pink- to purple-colored material between hepatocytes. The amorphous material was stained with direct fast scarlet (DFS), and green birefringent areas were observed under polarized light, confirming the presence of amyloid. A unique finding on the cytologic smear were macrophages containing amorphous and fibrillar amyloid-like protein. Histopathologic examination using H&E and Congo red staining confirmed amyloid deposits within the space of Disse, along the sinusoids, portal tracts, blood vessel walls, and within the cytoplasm of macrophages. Immunohistochemical staining with anti-AA amyloid antibodies further confirmed the presence of AA amyloid. To the author's knowledge, this is the first report of the cytologic finding of AA amyloid protein within macrophages and DFS stain detection of amyloid on a cytologic smear.