The distinction between transudates and exudates

Summary The first step in the diagnosis of pleural effusions is the distinction between exudates and transudates. The aim of this study was to evaluate the usefulness of various parameters for the differentiation of pleural exudates and transudates. We recorded clinical characteristics, final diagnoses, and measured pleural fluid and serum levels of albumin, protein, LDH, cholesterol, and bilirubin of 381 consecutive patients with pleural effusion. Seventy-one (23%) pleural effusions were transudates and 236 were exudates. As a single criterion, the pleural fluid to serum albumin ratio >0.5 was the most accurate parameter (88.4%). An albumin gradient of 12 g/l had an accuracy of 75% in the whole population but it detected 96% of transudative effusions in patients treated with diuretics. Light’s criteria and abbreviated Light’s criteria had similar accuracies, 87.8% vs. 88.2%, respectively. In conclusions, different alternatives can be used instead of Light’s criteria.     

Eicosanoid release and early changes in two acute non specific inflammatory reactions. Major role of prostacyclin and leukotrienes.

We have compared the early development (0-4h) of two acute non-specific inflammatory reactions induced by the intrapleural injection of isologous serum or a suspension of CaPP crystals. The intensity of the reactions was assessed in terms of the exudate volume, the number and ratio of pleural cells and different cell functions and secretions. The number of exudative cells elicited by isologous serum was higher than with CaPP but the PMN/Monocytes ratio was the same. The amount of protein in the serum-induced exudate was constant from 1 h to 4 h and was similar in the CaPP-induced pleural exudate at the latter time. The amount of complement increased similarly in the two models. The chemotactic potency of the exudates and cell supernatants following incubation showed similar values in the two models. Eicosanoid levels were higher in CaPP--than in isologous serum-induced exudates. Prostacyclin and peptidoleukotrienes were released in specially large amounts at the very outset of the inflammatory reactions.     

ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates.Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28).Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions.Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.     

Diagnostic value of ferritin in the differential diagnosis of malignant effusions

The diagnostic value of ferritin in pleural effusions or ascites was studied in 151 samples from 147 patients (four patients had both kind of effusions). Samples (99 pleural effusions, 52 ascites) were evaluated in 4 groups: benign transudate (27 cases), benign nontuberculous exudate (26 cases), tuberculous exudate (47 cases) and malignant exudate (51 cases). Median ferritin levels in effusions were 67 ng/ml, 805 ng/ml, 889 ng/ml, 998 ng/ml and median effusion/serum (E/S) ratios were 0.7. 2.0, 4.9, 3.2 respectively. There was a significant difference between the concentrations of ferritin in malignant (51 cases) and nonmalignant effusions (100 cases) (p < 0.001), but the specificity and positive predictive value were low (43% and 45% respectively). Ferritin levels in transudate group were significantly lower than those in the others (p < 0.001). However, ferritin concentrations in three exudate groups were similar (p > 0.05). When compared the all inflammatory effusions (malignant, tuberculous, nontuberculous inflammatory exudates) with noninflammatory effusions (transudate and exudate), we determined a significant difference (p < 0.001). CONCLUSIONS: 1) Elevated ferritin concentration in effusions is significant indicators of exudates; 2) It is not good a parameter to discriminate the malignant effusions from the benign ones; 3) They can be useful in the differential diagnosis of the inflammatory exudations from the noninflammatory ones.     

Pleural fluid lysozyme in human disease.

A prospective study was conducted to define the content, significance, and source of lysozyme present in the pleural fluid in human diseases. The pleural fluid lysozyme activity is similar in various malignant and nonmalignant transudates and exudates, and is of limited diagnostic value. The pleural fluid activity correlated well with that of paired serum samples but it had poor correlation with the disease state, the pleural fluid granulocyte counts, and total white blood cell counts. The data suggest that the pleural fluid lysozyme may be derived primarily from the blood and that it is not the product of inflammatory or neoplastic cells in the fluid itself.     

Phospholipid transfer protein activity is associated with inflammatory markers in patients with cardiovascular disease

Plasma phospholipid lipid transfer protein (PLTP) has several known key functions in lipoprotein metabolism. Recent studies suggest that it also may play a role in the inflammatory response. Inflammatory cell activity contributes to the development of atherosclerosis. To seek further evidence for the association of PLTP with inflammation, we studied the relationship between PLTP activity and five inflammatory markers [C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6), white blood cells (WBC), and fibrinogen] in 93 patients with low HDL and cardiovascular disease (CVD). Plasma PLTP activity had the strongest correlation with CRP (r=0.332, P<0.001) followed by SAA (r=0.239, P=0.021). PLTP, CRP, and SAA were significantly associated with body mass index (BMI), insulin or glucose, apolipoprotein (apo) B, and/or apo E level (r=0.264-0.393, P<0.01). PLTP, SAA, and IL-6 also were associated with the concentration of HDL particles without apo A-II [Lp(A-I)](r=0.373-0.472, P<0.005, n=56), but not particles with apo A-II. Smoking was associated with increased PLTP activity, CRP, and WBC, and hypertension with increased PLTP activity. In linear models, CRP remained significantly associated with PLTP after adjustment of CVD risk factors and insulin resistance. Also, much of the variability of plasma PLTP activity was explained by CRP, BMI, Lp(A-I), smoking, glucose, and blood pressure. These findings show for the first time that plasma PLTP activity is associated positively with CRP in CVD, a state of chronic inflammation.     

肺炎支原体肺炎患儿发生心血管系统损害的危险因素分析

目的:探讨肺炎支原体肺炎(MPP)患儿并发心血管系统损害的危险因素。方法:选取我院收治的241例MPP患儿为研究对象,收集患儿入院时的一般临床资料及实验室检查指标,按照是否并发心血管系统损害将患儿分为两组:心血管损害组和非心血管损害组,比较两组相关指标的差异,并对相关危险因素进行Logistic回归分析。结果:241例MPP患儿中有51例发生心血管系统损害(发生率21.2%);单因素分析提示:两组在年龄、急性期MP-Ab、胸腔积液、热程、血沉(ESR)、血清C反应蛋白(CRP)、白细胞计数(WBC)、血清CD4+/CD8+比值、发病7 d内应用大环内酯类药物、发病10 d内用药糖皮质激素存在统计学差异(P0.05);二分类非条件Logistic回归分析提示:年龄、热程、胸腔积液、CRP是MPP患儿发生心血管系统损害的独立危险因素(P0.05);血清CD4+/CD8+比值、发病7 d内应用大环内酯类药物则为保护性因素。结论:年龄、热程、胸腔积液、CRP是MPP患儿发生心血管系统损害的独立危险因素,而早期应用大环内酯类药物、及高CD4+/CD8+比值则为保护性因素,应当引起临床注意。     

Regulation of prostaglandin generation in carrageenan-induced pleurisy by inducible nitric oxide synthase in knockout mice

In the present study, by comparing the responses in wild-type mice (iNOSWT) and mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the correlation between endogenous nitric oxide (NO) and prostaglandin (PG) generation in carrageenan-induced pleurisy. The inflammatory response in iNOSKO mice was significantly reduced in respect to iNOSWT animals, as demonstrated by the exudate volume (-63%) and numbers of infiltrating cells (-62%). The levels of NOx in the pleural exudate from carrageenan-treated mice were significantly (p < 0.01) decreased in iNOSKO mice (16 +/- 7.6 nmoles/mice) compared to iNOSWT animals (133 +/- 9 nmoles/mice). Similarly, the amounts of PGE2 in the pleural exudates of carrageenan-treated animals were significantly (p < 0.01) lower in iNOSKO compared to iNOSWT mice (120 +/- 20 pg/mice vs. 308 +/- 51 pg/mice). Also the amounts of 6-keto-PGF(1 alpha) produced by lungs from carrageenan-treated iNOSKO mice (1.01 +/- 0.10 ng/tissue mg) were significantly (p < 0.01) reduced compared to iNOSWT carrageenan-treated mice (2.1 +/- 0.09 ng/tissue mg). In conclusion our results confirm, by the use of iNOSKO mice that in carrageenan-induced pleurisy NO positively modulates PG biosynthesis.     

Low-grade systemic inflammation profile, unrelated to homocysteinemia, in obese children

To investigate in prepubertal obese children (POC) the profile of chronic low-grade systemic inflammation (CLGSI) and its relation to homocysteinemia, 72 POC were evaluated for serum C-reactive protein (CRP) and amyloid A (SAA) levels, both markers of CLGSI, and plasma levels of total homocysteine (tHcy), an independent risk factor for adult atherosclerosis, in comparison to 42 prepubertal lean children (PLC). The main observations in POC were higher CRP levels compared to PLC, positive association of SAA levels to CRP levels, no association of CRP or SAA levels to tHcy levels. Thus, in POC, positively interrelated to each other, elevated CRP and unaltered SAA levels reveal a unique profile of the CLGSI, not explaining homocysteinemia-induced risk for future atherosclerosis.     

Generation of inflammatory cytokines in zymosan-induced pleurisy in rats: TNF induces IL-6 and cytokine-induced neutrophil chemoattractant (CINC) in vivo

Levels of inflammatory cytokines tumour necrosis factor (TNF), interleukin 1 (IL-1), IL-6, and cytokine-induced neutrophil chemoattractant (CINC), which is a member of the alpha-chemokine family in rats, were measured in the pleural exudates during zymosan-induced pleurisy to examine the relationship between the local production of cytokines and the inflammatory reaction. All four cytokine levels in the pleural exudate began to increase after 1-2 h, preceding the influx of neutrophils, and peaked after 4-5 h. Thereafter, these cytokine levels declined after 24 h, whereas the exudate volume still continued to increase and leukocyte number reached a plateau. Concomitant injection of actinomycin D (10 microg) with zymosan markedly suppressed the neutrophil infiltration, parallel with CINC production in the pleural exudate at 4 h. A transient elevation of IL-6 level, peaking at 5 h, and subsequent rise in the level of an acute-phase protein, T-kininogen, were also observed in the plasma. When recombinant human TNF-alpha (rhTNF-alpha) (20 000 U) was intrapleurally injected a rapid increase in pleural CINC level, followed by neutrophil infiltration, and a sharp rise in IL-6 level in the plasma, followed by an increase in T-kininogen, were demonstrated. These results suggest that CINC produced in the pleural exudate may participate in neutrophil infiltration, that IL-6 induced in the plasma stimulates T-kininogen production, and that endogenous TNF may be partly involved in the induction of CINC and IL-6 in this zymosan inflammation.     

Maternal and cord blood levels of serum amyloid A, C-reactive protein, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 during and after delivery

C-reactive protein (CRP) and serum amyloid A (SAA) are acute-phase proteins mainly synthesized by the liver in response to some cytokines. They are potentially useful to diagnosing infection and monitoring different clinical conditions. The aim of this study was to measure SAA and CRP in maternal and cord blood during and after delivery and try to correlate these proteins with tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8. Acute-phase proteins and cytokines were measured by ELISA in 24 healthy pregnant women undergoing vaginal delivery or Cesarean section. Cord blood samples in addition to maternal blood were collected. SAA and CRP reached the maximum maternal serum levels 24 hours after delivery, while cytokines remained constant over time. SAA and CRP were significantly higher in maternal serum than in newborn's (P< .001) at the moment of delivery. SAA and CRP, regardless of the type of delivery, reproduce the common pattern observed in most inflammatory conditions. Proinflammatory cytokine serum levels do not mirror the increase in SAA and CRP levels.     

Sequential thoracentesis: minor change of zinc compared to other selected essential trace elements in the serum

This study first indicates that the serum trace element Zn tends to decrease in the course of sequential thoracenteses. Other selected essential elements such as copper (Cu), manganese (Mn), molybdenum (Mo), and cobalt (Co) do not reveal loss changes in their serum levels. Therefore, Zn should be monitored in patients who undergo repeated thoracentesis. To measure the magnitude of changes in serum trace elements and the clinical relevance of potential imbalances, concentrations of the essential elements are analyzed in 57 serum/effusion pairs obtained from 5 patients (4 male, 1 female; age 28–78 yr) who underwent repeated thoracenteses as a result of recurrent pleural effusion. All patients declined other therapeutic options such as chemical pleurodesis and /or chest tube placement. The total volumes of fluid removed ranged from 2.3 to 19.3 L and the frequency of thoracentesis ranged from 6 to 15 within a period of 102–174 days. Two patients had benign pleural disease and three had malignancies. Three patients suffered from pleural effusions resulting from exudates (total protein content >3.0 g/dL, LDH >200 U/L), and two resulting from transudates (total protein <3.0 g/dL, LDH <200 U/L). All trace elements were simultaneously determined by inductively coupled argon plasma-mass spectrometry. In addition, the concentrations of the following clinically relevant parameters were analyzed by standard methods: total protein, pH, leukocyte count, lactate dehydrogenase, and glucose.     

Acidocillin concentration in middle ear exudate]

Acidocillin levels were determined in the middle ear exudates and serum of patients with acute exudative otitis media after oral administration of the drug. Acidocillin rapidly diffused exudate into the ear and its level in the exudate in 1 hour was 0-1.7 gamma/ml. At the same time the serum levels ranges within 4 to 25 gamma/ml. acidocillin remained longer in the ear exudate than in the serum. In 12 hours 0.2 to 1.3 gamma/ml of acidocillin was still found in the exudates, while there was no antibiotic in the serum.     

脓毒症患儿血清SAA、PCT、CRP水平与预后的关系及其诊断价值分析

摘要 目的：探讨脓毒症患儿血清淀粉样蛋白A（SAA）、降钙素原（PCT）、C反应蛋白（CRP）与预后的关系,并分析三者对脓毒症的诊断价值。方法：纳入我院于2016年8月～2020年6月期间收治的脓毒症患儿60例开展回顾性研究,作为脓毒症组,选取同期于我院进行体检的健康儿童40例作为对照组,比较两组血清SAA、PCT、CRP水平。根据脓毒症患儿1个月内的生存、死亡情况,分成生存组（n=42）、死亡组（n=18）,比较两组临床资料及血清SAA、PCT、CRP水平,经COX回归模型分析脓毒症患儿死亡的危险因素。绘制受试者工作特征（ROC）曲线分析血清SAA、PCT、CRP对脓毒症的诊断价值。结果：脓毒症组血清SAA、PCT、CRP水平显著高于对照组（P＜0.05）。死亡组器官障碍数量＞2个、脓毒性休克患儿占比分别为55.56%、44.44%,显著高于生存组的19.05%、9.52%（P＜0.05）;死亡组入院后1 h内使用抗菌治疗患儿占比为38.89%,显著低于生存组的69.05%（P＜0.05）;死亡组血清SAA、PCT、CRP水平高于生存组（P＜0.05）。COX多因素分析结果显示,器官障碍数量＞2、脓毒性休克及血清SAA、PCT、CRP水平升高是脓毒症患儿死亡的危险因素（P＜0.05）,而入院后1 h内使用抗菌治疗是脓毒症患儿死亡风险的保护性因素（P＜0.05）。血清SAA、PCT、CRP单独及三者联合诊断脓毒症的曲线下面积（AUC）分别为0.808、0.780、0.761、0.912。结论：脓毒症患儿血清SAA、PCT、CRP明显升高,三者升高均为脓毒症患儿死亡的危险因素,且对脓毒症具有一定诊断价值。     

Intraperitoneal amyloid formation by amyloid enhancing factor--rich macrophages in ascitic fluid.

Although resident peritoneal cells from amyloidotic mice (amyloidotic peritoneal cells) are capable of processing the precursor protein of secondary amyloidosis, serum amyloid A (SAA) to amyloid fibrils, the peritoneum is a rare site for amyloid deposition. This is considered to be due to a deficiency of SAA in the peritoneum. To increase the supply of SAA to the peritoneum, ascitic fluid containing about the same protein constituents as in the serum was induced in mice. Amyloidotic peritoneal cells were packed in a microchamber which was shielded with filter membranes, and cultured in ascitic fluid supplemented with additional inflammatory factors. On the 7th day, Congo red-positive structures which showed green birefringence under polarized light were found inside and occasionally outside the chamber. By anti-AA or -SAA immunostaining, amyloid deposits and the cell surfaces of macrophages were positive. Immunologic depletion of T- and B-lymphocytes from the amyloidotic peritoneal cells did not adversely effect the amyloid formation in microchambers. These results suggest that either ascitic fluid containing sufficient amounts of SAA, or peritoneal macrophages with a high amyloid enhancing factor (AEF) activity are indispensable for AA amyloid fibrillogenesis in the peritoneum.     

Changes in CRP, SAA and haptoglobin produced in response to ovariohysterectomy in healthy bitches and those with pyometra

The aim of the study was to assess changes in serum C-reactive protein (CRP), serum amyloid A component (SAA) and haptoglobin (Hp) concentrations in healthy bitches and in those with pyometra undergoing ovariohysterectomy, and to establish the usefulness of such determinations for monitoring the postoperative period. Our results indicate that CRP and SAA determinations serve to evaluate the severity of the inflammatory process in pyometra since the concentrations of these acute phase proteins were increased immediately after surgery and diminished thereafter. The CRP and SAA response was rapidly produced while Hp concentrations increased in a more gradual manner. Thus, postoperative concentrations of CRP and SAA provide valuable information on the subsidence of the inflammatory response during the uneventful postoperative period. Our findings also suggest that acute phase proteins might be useful diagnostic markers of early postoperative complications.     

Roles of leukotrienes in two rat allergic inflammatory models; IgE-mediated and IgG-antigen complex-induced pleurisies

Rat IgE pleurisy was induced by the injection of di-nitrophenol-conjugated bovine serum albumin (DNP-BSA) 48 hours after the intrapleural injection of rat anti-DNP-IgE serum. IgG-BSA complex pleurisy was also induced by the intrapleural injection of IgG-BSA complexes produced at the optimum ratio in vitro. Plasma exudation was markedly increased in the first 20 minutes, but not observed thereafter, in IgE pleurisy, whereas marked plasma exudation in the first 20 minutes was followed by weak exudation at three and five hours in IgG-BSA complex pleurisy. Leukotrienes (LTs) E4 (100 ng/rat), D4 (32) and B4 (16) were detected on HPLC in the pleural exudate in the first 20 minutes of IgG-BSA complex pleurisy, but less (9 ng/rat) LTE4 alone was detected in the five-hour exudate. The first 20-minute pleural exudate contained 13 ng/rat of LTE4 in IgE pleurisy. The plasma was completely inhibited by simultaneous treatment of rats with pyrilamine (2.5 mg/kg, i.p.) and methysergide (3 mg/kg, i.p.), as it was in compound 48/80-induced pleurisy. In IgG-BSA complex pleurisy, 90% of the pleural exudate for the first 20 minutes was inhibited by the same treatment, and the rest was completely suppressed by simultaneous treatment with an intrapleural injection of AA-1777, a selective 5-lipoxygenase inhibitor. AA-1777 alone did not reduce the plasma exudation significantly. The 5-lipoxygenase inhibitor was also very effective in reducing the migrating numbers of polymorphonuclear and mononuclear leukocytes to half, without affecting the eosinophils of mast cells.     

Effect of Zinc Sulfate and Zinc Glycine Chelate on Concentrations of Acute Phase Proteins in Chicken Serum and Liver Tissue

Biological Trace Element Research - The aim of the study was to determine how inorganic and organic forms of zinc affect the concentrations of C-reactive protein (CRP), serum amyloid A (SAA),...     

Concentrations of C-reactive protein,serum amyloid A,and haptoglobin in uterine arterial and peripheral blood in bitches with pyometra

Pyometra is a life-threatening reproductive disorder that affects the uterus of female dogs. This study was designed to identify the possible indicators of uterine inflammation by comparing C-reactive protein (CRP), serum amyloid A (SAA), and haptoglobin (Hp) concentrations in uterine arterial and peripheral venous blood in bitches with open- and closed-cervix pyometra. CRP, SAA, and Hp concentrations were higher in bitches with closed-cervix pyometra irrespective of the site of blood collection. Higher acute-phase protein concentrations were observed in peripheral compared with uterine arterial blood in bitches with closed-cervix pyometra, whereas the levels were comparable in dogs with open-cervix pyometra. Our results indicate that mean acute-phase protein concentrations differ according to pyometra type/severity and blood source and suggest the possible use of peripheral blood levels of CRP, SAA, and Hp to monitor inflammation during the course of pyometra.