Usefulness of Non-invasive Markers for Predicting Significant Fibrosis in Patients with Chronic Liver Disease

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

A study of plasma alpha-2-macroglobulin levels in type 2 diabetic subjects with microalbuminuria.

BACKGROUND: Alpha-2 macroglobulin (Alpha-2-M) is a major plasma protease inhibitor that also regulates the activity of a variety of bioactive peptides including interleukins and exerts a range of immunomodulatory effects. OBJECTIVE: We conducted the present study with the objective to study the alpha-2-M levels in type 2 diabetic subjects with microalbuminuria in an attempt to establish alpha-2-M as a predictor of microvascular complications in diabetes. MATERIAL AND METHODS: Plasma Alpha-2-M levels were assayed in 100 (53 males and 47 females) randomly selected type 2 diabetic subjects with microalbuminuria. Diabetes was diagnosed according to the expert committee report of 1998. Patients with any acute metabolic complication like hypoglycemia, ketoacidosis, cerebrovascular accident or any acute infection were not included in the study group. RESULTS: Majority of patients belonged to 40-60 years age group. In our study alpha-2-M levels indicated a clear increase in diabetic subjects with the increasing age of subjects confirmed by multiple logistical analysis. Alpha-2-M levels were not found to be significantly different between males and females (55.6 +/- 11.3 vs. 53.7 +/- 10.5). Duration of diabetes was found to be an important confounding variable showing a direct positive correlation with alpha-2-M levels and also a significant correlation was found between alpha-2-M levels with different levels of microalbuminuria on multiple logistical analysis. No significant relation of alpha-2-M levels with either fasting blood sugar or HbA1 was observed. CONCLUSION: The increase in plasma alpha-2 macroglobulin levels in diabetes may be a correlative measure to encounter the potential proteolytic challenge associated with diabetic microangiopathy, even very early in the course of the disease. Alph-2 macroglobulin may yet be one of the most specific markers of microvascular complications in diabetes than any other serum protein.

Alpha2 Macroglobulin, biological and clinical relevance

Alfa2-macroglobulina es una proteína plasmática de alto peso molecular que juega un papel importante como inhibidor de proteinasa durante la respuesta imflamatoria. Esta molécula única es capaz de unirse a prácticamente todas las grandes clases de proteinasas, y estudios recientes demuestran su cpacidad adicional de unirse a un grupo grande y diverso de ligandos. La función(es) exacta de A2M aún es desconocida, pero ha sido implicada como participante importante en diversas actividades biológicas. Es escasa la información clínica sobre A2M, y en México no se ha realizado ninguna investigación en ésta área. Aquí presentamos una revisión breve sobre la biología de A2M y describimos un estudio inicial y exploratorio diseñado para examinar los niveles normales de A2M en nuestra población y para determinar una posible relación entre A2M y ciertas enfermedades

Studies on the components of the contact phase system in patients with acute nonlymphoblastic leukemia

The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, Sao Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not elegible, according to the exclusion criteria: infection/septicemia, previous treatment of blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p=0.02) and prealbumin (p=0.03) were significantly decreased, and prothrombin time increased (p=0.003) in the patient group when compared to the control. Significant correlation (r=0.49, critical value=0.43, p<0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r=0.54, critical value=0.44, p<0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by the Willcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.

A study of antitrypsin and macroglobulin levels in serum and saliva of patients with gingivitis.

Periodontal diseases are associated with chronic inflammation. The destruction of connective tissue matrix is responsible for the pathogenesis of chronic inflammatory states. The degradation of matrix is initiated extra and pericellularly by proteinases produced locally at the inflammatory site. The regulation of these proteinases are by inhibitors present in serum and extravascular tissues, and it is the proteinase/proteinase inhibitor balance that determines the progression of chronic inflammatory state. Few contradicting studies are available on changes in the levels of proteinase inhibitors in serum in periodontal disease. The occurrence of these inhibitors in saliva has not been studied in detail. The present study was aimed at measuring the Proteinase inhibitors in serum and saliva of patients with periodontal disease.

An inhibition ELISA to determine alpha macroglobulin levels in mouse plasma

A sensitive method for quantifying mouse plasma alpha-macroglobulins (AM) using an inhibition ELISA is described. AM are important plasmaproteinase inhibitors that possibly act also as immunomodulatory molecules. The standard protocol develope in our experiments involves coating well with 10 µg/ml A2M in carbonate buffer, followed by incubation with a 1:1 (v/v) mixture of the plasma to be tested (diluted 1/1000) and goat anti-AM (diluted 1/1250). This is followed by further incubation, first with the enzyme-conjugated antibody and with the substrate prior to the reading of absorbance levels of the reaction products. Standard curve samples must be included in each plate, employing known amounts of the purified Murine Alpha-2-Macroglobulin (MuA2M) used for coating, with concentrations ranging from 0.001 to 10 µg/ml. Using test samples in triplicates and a 6-point standard curve in a single ELISA plate, 25 plasma samples can be tested accurately. The method offers an useful tool for establishing AM levelsin small samples of mouse plasma

Valores de referencia de fracciones séricas específicas en adultos / Determination of specific sera protein fractions in adults

Con el objeto de determinar valores de referencia de fracciones séricas específicas en adultos por el método de inmunodifusión radial sobre placas Diffu-Plate (Biocientífica S.A.), se seleccionó al azar una población mayor de 18 años. Sobre esta muestra poblacional (n=50) se determinó la concentración sérica de albúmina, a2 macroglobulina, ceruloplasmina, haptoglobina, transferrina, apolipoproteínas AI y B, Fracciones C3 y C4 de complemento e inmunoglobulina A. Los resultados se compararon con los hallados en la bibliografía nacional e internacional

Diagnostic and prognostic utility of C-reactive protein, alpha-1-antitrypsin and alpha-2-macroglobulin in neonatal sepsis: a comparative account.

C-reactive protein (CRP), alpha-1-antitrypsin (alpha-1-AT) and alpha-2-macroglobulin (alpha-2-MG) levels were evaluated serially in 25 healthy and 20 septicemic neonates and then compared as early diagnostic aids and prognostic indicators in this illness. Compared to healthy controls, septicemic neonates had significantly higher mean CRP levels (p less than 0.01). Neonates with septicemia, who recovered, had higher mean CRP levels than the group which died (p less than 0.05). As an early diagnostic aid CRP had a low Youden index, whereas for prognosis its index was higher. Septicemic neonates also had significantly higher mean alpha-1-AT levels (p less than 0.05), 12-24 hours after onset of illness, as compared to healthy neonates. Alpha-1-antitrypsin could not be used as an early diagnostic aid in septicemia, but was useful for predicting outcome. Mean alpha-2-macroglobulin levels did not show significant variation in healthy and septicemic neonates. Lower mean alpha-2-MG levels were observed in neonates recovering from septicemia. As an early diagnostic aid alpha-2-MG had a low Youden index, whereas for prognosis its index was higher. CRP had a higher Youden index than alpha-2-MG for early diagnosis of neonatal septicemia and had a higher index than both alpha-1-AT and alpha-2-MG for predicting outcome in septicemia. Serial use of CRP alone is, therefore, recommended for both purposes.

Serum protease inhibitors in opisthorchiasis, hepatoma, cholangiocarcinoma, and other liver diseases.

Serum alpha 1-antitrypsin, alpha 1-antichymotrypsin and alpha 2-macroglobulin increased significantly in patients suffering from liver diseases: hepatoma, amoebic liver abscess, hepatitis, hepatic cirrhosis, cholangiocarcinoma, carcinoma of the head of pancreas including liver fluke infection (opisthorchiasis). Marked increase of alpha 1-antitrypsin and alpha 1-antichymotrypsin were found in cholangiocarcinoma, carcinoma of the head of pancreas, amoebic liver abscess, hepatic cirrhosis and hepatoma. alpha 2-macroglobulin increased markedly in hepatic cirrhosis. The concentrations of protease inhibitors found in opisthorchiasis were only moderately elevated.

DHF characterized by acute type DIC with increased vascular permeability.

Decreases in platelet count, fibrinogen concentration, factor VIII, antithrombin III and alpha 2-antiplasmin activities, increase in FDP-D fraction, and pleural effusion were observed transiently at early fever stage of DHF at grade II, indicating DHF patients had manifestations of the acute type of DIC with increased permeability of vascular wall.

Estudio metodológico de la determinación de alfa-2-macroglobulina en suero / Methodologic study for the determination of alpha-2-macroglobulin in serum

Se realiza el montaje y estandarización de un nuevo método cromogénico para medir los niveles séricos de alfa-2-macroglobulina (alfa-2 M) utilizando Kit comercial desarrollado por la firma Boehringer Mannheim. El método resulta rápido, sencillo y requiere recursos que están disponibles en la mayor parte en los laboratorios. La sensibilidad y los coeficientes de repetibilidad y reproducibilidad resultan satisfactorios, teniendo en cuenta el nivel sérico de este parámetro y su variabilidad en condiciones patológicas. La evaluación retrospectiva de la exactitud y la precisión del método en nuestro laboratorio resultó ser muy satisfactoria. Se aplicó el procedimiento a 2 poblaciones de sujetos normales y diabéticos y se encontraron niveles de alfa-2 M significativamente diferentes. Se señalan las conclusiones