OBJECTIVETo study the diagnostic value of determinations of serum acute phase reaction protein, such as complement 3 (C3), complement 4 (C4), prealbumin (PA) and C-reactive protein (CRP), etc., in patients with severe acute respiratory syndrome (SARS).

METHODSSerum levels of C3, C4, PA and CRP were determined by turbidimetry in 54 cases of SARS, 20 of other pneumonia and 30 normal persons.

RESULTSSerum concentrations of C3, C4, CRP and PA were (1.18 +/- 0.42) g/L, (1.15 +/- 0.56) g/L, (10.52 +/- 8.77) mg/L and (107 +/- 54) mg/L in SARS patients, (1.30 +/- 0.46) g/L, (0.57 +/- 0.31) g/L, (0.88 +/- 0.43) mg/L and (291 +/- 76) mg/L in patients with other pneumonia, and (1.11 +/- 0.56) g/L, (0.38 +/- 0.26) g/L, (0.42 +/- 0.26) mg/L and (376 +/- 74) mg/L in normal persons, respectively. Serum level of PA was significantly lower and levels of C4 and CRP significantly in patients with SARS higher than those in patients with other pneumonia and normal persons (P < 0.01). There was no significant difference in serum level of C3 between the three groups (P > 0.05).

CONCLUSIONDetermination of serum level of C4, CRP and PA in suspected patients is beneficial to early differential diagnosis for SARS.

Acute-Phase Proteins ; analysis ; Acute-Phase Reaction ; blood ; Adult ; Aged ; C-Reactive Protein ; analysis ; Complement C3 ; analysis ; Complement C4 ; analysis ; Female ; Humans ; Male ; Middle Aged ; Prealbumin ; analysis ; Severe Acute Respiratory Syndrome ; blood

This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1x10(3) and 1x10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-alpha, and IFN-gamma were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 microg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-alpha and IFN-gamma with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.
Acute-Phase Proteins/*analysis ; Animals ; Blood Chemical Analysis ; Coccidiosis/*immunology/*pathology ; Disease Models, Animal ; Eimeria/*pathogenicity ; Goats ; Histocytochemistry ; Inflammation Mediators/*analysis

The purpose of our study was to investigate changes in immunological parameters induced by weaning stress (including milk restriction) in calves. Fifteen Holstein calves were subjected to weaning at 6 weeks of age. Blood samples were collected at -14, -7, -2, 1, 3, and 5 days post-weaning (DPW; 0 DPW = 42 days). Weaning caused significant (p < 0.01) increases in the neutrophil (NE):lymphocyte (LY) ratio at 5 DPW with a significant (p < 0.05) reduction of LYs. The concentration of acute-phase proteins (haptoglobin and serum amyloid A) also increased significantly (p < 0.05) at 3 and 5 DPW compared to -2 DPW. Levels of the iron-binding protein lactoferrin decreased significantly (p < 0.05) after weaning. Serum tumor necrosis factor-alpha and cortisol levels were elevated (p < 0.05) at 3 DPW, while those of serum interferon-gamma decreased (p < 0.05) at 1 and 3 DPW compared to levels observed before weaning. Weaning significantly (p < 0.05) decreased the percentage of CD25+ T cells in the peripheral blood. In conclusion, weaning stress affected the NE:LY ratio along with the levels of acute phase proteins, lactoferrin, cortisol, and inflammatory cytokines in the peripheral blood of calves. Weaning stress may induce an acute phase response possibly through the elevation of cortisol production and modulation of inflammatory cytokines.
Acute-Phase Proteins/*immunology/metabolism ; Acute-Phase Reaction/immunology/*veterinary ; Animals ; Cattle/*immunology ; Female ; Flow Cytometry ; Haptoglobins/analysis/immunology ; Hydrocortisone/blood/immunology ; Interferon-gamma/blood/immunology ; Lactoferrin/analysis/immunology ; Leukocyte Count/veterinary ; Leukocytes/cytology/*immunology ; Male ; Serum Amyloid A Protein/analysis/immunology ; Stress, Physiological/*physiology ; Tumor Necrosis Factor-alpha/blood/immunology ; Weaning

OBJECTIVETo investigate the protective effect of recombinant human N-terminal lipopolysaccharide binding protein in mice challenged with LPS.

METHODSSeventy male Kunming mice were randomly divided into 3 groups, i.e. LPS challenge (Injection of LPS into abdominal cavity, n = 21); tLBP protection (Injection of LPS and tLBP into abdominal cavity, n = 21) and control (Injection of normal saline into abdominal cavity, n = 8) groups. The blood samples and tissue samples of the liver and lungs were harvested on 15 and 30 minutes and 1, 3, 6, 12 and 24 hours after the injection. The serum contents of ALT and TNF-alpha were determined by biochemical velocity analysis and RIA method, respectively. The pathomorphological changes in the liver and pulmonary tissue were examined under light microscope (LM). The mortality rate of ten mice each was observed within 24 hours after the injection of tLBP + 400 ng LPS or 400ng LPS.

RESULTSThe ALT content of tLBP group reached the peak level at 12 post-injection hour (PIH) (41.00 +/- 4.58), but it was significantly lower than that in LPS group in which it peaked at 6PIH (99.50 +/- 62.63) (P < 0.01). The TNF-alpha content in tLBP and LPS group was lower than that in LPS group, and both reached the peak level at 3 PIH (35.96 +/- 7.33). Compared with those in LPS, injury to hepatocytes in tLBP group was obviously milder without scattered necrosis. The pulmonary congestion in tLBP group was abated, and the inflammatory exudation in the alveoli was evidently less than that in LPS group. There were 9 out of 10 mice died in the LPS challenge group, while only 3 out of 10 mice died during 24 hours after LPS injection in tLBP protection group.

CONCLUSIONPreliminary results indicated that recombinant human tLBP might possess biological activity with a potential protection effect in LPS challenged mice.

Acute-Phase Proteins ; Animals ; Carrier Proteins ; therapeutic use ; Lipopolysaccharides ; toxicity ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; Membrane Glycoproteins ; Mice ; Random Allocation ; Recombinant Proteins ; pharmacology ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo investigate the expression of lipopolysaccharide binding protein (LBP) and its gene in rats with endotoxemia and explore the role of LBP in the response of host to endotoxin.

METHODSThirty Wistar rats were divided randomly into five groups: the normal group and the endotoxemia groups (1, 3, 6, 12 hours after LPS injection, respectively). The level of plasma endotoxin was determined by the Limulus Amebocyte Lysate assay. The expression of LBP mRNA in hepatic tissue was examined by reverse transcription polymerase chain reaction (RT-PCR). Plasma levels of LBP, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay (ELISA). Morphologic changes of hepatic tissue were observed under transmission electron microscope.

RESULTSThe level of plasma endotoxin peaked at 1 h after LPS injection, then declined, but was still higher than that of the normal group at 12 h; intrahepatic expression of LBP mRNA and plasma LBP increased with time after LPS stimulation; TNF-alpha and IL-6 in plasma increased with upregulation of LBP expression; there were significant differences between the normal group and endotoxemia groups (P<0.05). Activation of Kupffer cells and injury of hepatocytes could be seen in rats with endotoxemia.

CONCLUSIONSLPS can upregulate the intrahepatic expression of LBP mRNA and increase the plasma LBP level. Under certain conditions, LBP may enhance the sensitivity of host to the toxic effects of LPS.

Acute-Phase Proteins ; Analysis of Variance ; Animals ; Carrier Proteins ; genetics ; metabolism ; Endotoxins ; blood ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Interleukin-6 ; metabolism ; Membrane Glycoproteins ; Microscopy, Electron ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism ; Up-Regulation

Previous studies reported the beneficial effect of erythropoietin (EPO) in acute injuries. We followed patients with and without acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and evaluated the effect of EPO on long-term outcome. We also assessed the efficacy of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. Seventy-one patients scheduled for elective CABG were randomly given either 300 U/kg of EPO or saline before CABG. The primary outcome was AKI, and the secondary outcome was the all-cause-mortality and composite of all-cause-mortality and end stage renal disease (ESRD). Twenty-one patients had AKI, 14 (66.7%) in the placebo group and 7 (33.3%) in the EPO group (P = 0.05). Also, uNGAL was higher in the patients with AKI than in those without AKI at baseline, 2, 4, 24, and 72 hr after CABG (P = 0.011). Among patients with AKI, 2-week creatinine (Cr) was not different from baseline Cr in the EPO group, but 2-week Cr was significantly higher than baseline Cr in the placebo group (P = 0.009). All-cause-mortality (P = 0.022) and the composite of all-cause-mortality and ESRD (P = 0.003) were reduced by EPO. EPO reduces all-cause-mortality and ESRD in patients with AKI, largely due to the beneficial effect of EPO on recovery after AKI.
Acute Kidney Injury/etiology/mortality/*prevention & control ; Acute-Phase Proteins/urine ; Aged ; Aged, 80 and over ; Biological Markers/urine ; Coronary Artery Bypass/*adverse effects ; Creatinine/analysis ; Double-Blind Method ; Erythropoietin/*therapeutic use ; Female ; Hematinics/*therapeutic use ; Humans ; Kaplan-Meier Estimate ; Lipocalins/urine ; Male ; Middle Aged ; Placebo Effect ; Prospective Studies ; Proto-Oncogene Proteins/urine ; ROC Curve ; Recombinant Proteins/therapeutic use ; Risk Factors ; Treatment Outcome

OBJECTIVETo isolate and purify a new type of lipopolysaccharide binding protein (LBP) from burn rabbit serum, and to investigate its biological functions.

METHODSRabbits subjected to burn injury and endotoxemia were employed. The serum from the rabbits was purified by two-steps of ion-exchange chromatography (Bio-Rex 70 Resin, Mono-Q) and gel chromatography. Furthermore, the serum was identified by flow cytometry analysis, agglomeration test with sheep erythrocyte, and amino end amino acid residue sequencing. The obtained protein was applied to cultured human monocytes (U937), and the cytokine secretion such as TNFalpha from the U937 was observed.

RESULTSThe molecular weight of the harvested protein was 48 kDa, and the 10 amino acid sequence at N end was arranged as GSQGTFTSEE, which was different to the amino acid sequence in NCBI protein bank and was so named P48. P48 possessed similar function to that of LBP and could promote the binding of LPS in a very low concentration with peripheral blood monocytes (PBMC), and also promote the TNFalpha secretion from U937.

CONCLUSIONP48, a new type of LBP, could be isolated and purified from the burn rabbit serum. P48 possessed similar biological activities to that of LBP and could promote the process of inflammatory reaction.

Acute-Phase Proteins ; Amino Acid Sequence ; Animals ; Binding, Competitive ; drug effects ; Blood Proteins ; chemistry ; isolation & purification ; pharmacology ; Burns ; blood ; Carrier Proteins ; chemistry ; isolation & purification ; pharmacology ; Chromatography, Gel ; Chromatography, Ion Exchange ; Female ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; cytology ; drug effects ; metabolism ; Lipopolysaccharides ; metabolism ; Male ; Membrane Glycoproteins ; Rabbits ; Sequence Analysis, Protein ; Tumor Necrosis Factor-alpha ; secretion ; U937 Cells

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.
Acute-Phase Proteins/*urine ; Adult ; Biomarkers/blood/urine ; Biopsy ; Chi-Square Distribution ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology/*urine ; Humans ; Kaplan-Meier Estimate ; Kidney/*metabolism/pathology/physiopathology ; Lipocalins/*blood/*urine ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood/*urine ; Retrospective Studies ; Risk Factors ; Young Adult

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.
Acute-Phase Proteins ; Adolescent ; Adult ; Aged ; Biomarkers/blood ; Biopsy ; Chi-Square Distribution ; Creatinine/blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology ; Humans ; Kidney/*metabolism/pathology/physiopathology ; Linear Models ; Lipocalins/*blood ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood ; Renal Insufficiency, Chronic/blood/etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Young Adult