Marcadores de fase aguda en niños y adolescentes obesos con trastornos metabólicos / Acute phase markers in obese children and adolescents with metabolic disorders

Introducción. La obesidad es un problema de salud pública mundial y la enfermedad crónica no transmisible más frecuente. Se asocia con la elevación de proteínas inflamatorias de fase aguda y citocinas proinflamatorias. Objetivo. Evaluar los niveles de proteínas de fase aguda en niños y adolescentes obesos con esteatosis hepática y síndrome agudo metabólico. Metodología. Se incluyeron 45 niños con índice de masa corporal ≥ percentil 95, de edades entre 5,0 y 15,5 años. Se determinaron reactantes de fase aguda: proteína C reactiva, haptoglobina, a-2 macroglobulina y apolipoproteína A-1, y se realizó una ecografía para evaluar la esteatosis hepática. Resultados. Todos los pacientes mostraron una elevación de proteína C reactiva. Los pacientes con síndrome metabólico también tuvieron un incremento en la apolipoproteína A-1 y la haptoglobina. Los pacientes con esteatosis hepática tuvieron un aumento significativo en la a-2 macroglobulina además de la protenína C reactiva.

Introduction. Obesity is a worldwide public health problem and the most common non-communicable chronic disease. It is associated with an increase in inflammatory acute phase proteins and proinflammatory cytokines. Objective. To assess the levels of acute phase proteins in obese children and adolescents with hepatic steatosis and metabolic syndrome. Methodology. Forty-five children with a body mass index ≥ 95th percentile aged 5.0-15.5 years were included. The following acute phase reactants were determined: C-reactive protein, haptoglobin, alpha-2-macroglobulin, and apolipoprotein A-1; besides, an ultrasound was done to assess hepatic steatosis. Results. C-reactive protein levels increased in all patients. Patients with metabolic syndrome also had high levels of apolipoprotein A-1 and haptoglobin. Patients with hepatic steatosis had a significant increase in alpha-2-macroglobulin in addition to high C-reactive protein.

Serum profiles of extracellualr matrix degradation inhibitors across the stages of liver fibrosis in chronic hepatitis C patients

Tissue inhibitor metalloproteinase-1 [TIMP-1] and alpha-2 macroglobulin [AMG] are extracellular matrix degeneration inhibitors that have been demonstrated to increase with liver fibrosis. However, date are lacking regarding their patterns of change. This study analyses their detailed serum profile across liver fibrosis stages in chronic hepatitis C [CHC]. Serum TIMP-1 and AMG measurements were evaluated for 78 adult male CHC patients versus liver fibrosis [F] stages [METAVIR F0-F4]. The performance characteristics for discrimination of sequential [close stages], significant [F >/= 2], and advanced [F >/= 3] fibrosis were assessed. Both TIMP-1 and AMG correlated significantly with fibrosis [r=0.31, p=0.005; r=0.37, p=0.001, respectively], but failed to discriminate sequential stages. For discrimination of significant fibrosis, the areas under receiver operating characteristics curves were small [0.59 and 0.57, respectively]. T a cut-off value of 743 ng/ml, TIMP-1 showed a 100% specificity [with 17.6% sensitivity], while at a cut-off of 3 gm/l, AMG showed 73.5% sensitivity [with 36.4% specificity]. A similarly modest discrimination was noted for advanced fibrosis. Interestingly, AMG showed an early rise with significantly higher values in F0 compared with healthy controls [3.6 +/- 1.1 vs. 1.8 +/- 0.6, respectively]. Neither TIMP-1 nor AMG could discriminate the sequential stages of fibrosis. Their modest performances for discrimination of significant and advanced fibrosis are related to the wide normal range f TIMP-1 and the early rise of AMG. A longitudinal monitoring would give a better understanding of their true changes, and examine whether patients having high AMG levels at F0 would be fast fibrosers or respond differently to therapy

Proteomic Identification of Proteins Suggestive of Immune-Mediated Response or Neuronal Degeneration in Serum of Achalasia Patients

BACKGROUND/AIMS: The primary pathophysiologic abnormality in achalasia is known to be a loss of inhibitory myenteric ganglion cells, which may result from an immune-mediated response or neuronal degeneration. The aim of this study was to identify proteins suggestive of an immune-mediated response or neuronal degeneration in the serum of achalasia patients using a proteomic analysis. METHODS: Blood samples were collected from five symptomatic achalasia patients and five sex- and age-matched healthy controls. Serum proteomic analysis was conducted, and the protein spots were identified using matrix-assisted laser desorption ionization/time-of-flight and a proteomics analyzer. The serum level of C3 was measured by enzyme-linked immunosorbent assay in nine patients with achalasia and 18 sex- and age-matched healthy controls. RESULTS: Of the 658 matched protein spots, 28 spots were up-regulated over 2-fold in the serum from achalasia patients compared with that from controls. The up-regulated proteins included complement C4B5, complement C3, cyclin-dependent kinase 5, transthyretin, and alpha 2 macroglobulin. The serum levels of C3 in achalasia patients were significantly higher than those of controls. CONCLUSIONS: The serum proteomic analysis of achalasia patients suggests an immune-mediated response or neuronal degeneration. Further validation studies in larger samples and the esophageal tissue of achalasia patients are required.

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.

preliminary study of inflammatory markers in non-alcoholic steatohepatitis patients

It was reported that C-reactive protein [CRP] levels increase in parallel with the progression of chronic liver diseases, such as chronic hepatitis and liver cirrhosis. Inflammatory markers, such as high sensitive C-reactive protein [hsCRP], ferritin, transferrin, albumin, alpha-1 acid glycoprotein [AAG], alpha-2 macroglobulin [AMG], alpha-1 anti-trypsin [AAT] and lipoprotein a [Lp[alpha]] were measured in coronary artery disease patients [CAD] and CAD patients with non-alcoholic steatohepatitis [NASH]. In the present preliminary study an attempt was made to study whether there is an increase in the levels of CRP in CAD patients associated with NASH. CAD patients showed an increase in CRP and serum ferritin levels. In CAD patients with NASH along with an increase in the levels of serum ferittin [p<0.001], the levels of serum AMG and ceruloplasmin [CP] were also increased [p<0.01]. The CAD patients with NASH had a higher proportion of diabetes, hypertension and dyslipidaemia compared to CAD patients. But how this difference contributes to the elevation in acute inflammatory markers particularly AMG and CP levels in CAD patients with NASH cannot be explained. This study shows that a substantial number of CAD patients may be associated with NASH. Non-invasive simple parameters that reflect the degree of inflammation and fibrosis of the liver in patients with NASH would facilitate improved understanding and treatment of the disease. Further studies may be necessary to evaluate the percentage of NASH patients progressing to CAD

Circulating apolipoprotein alpha1, haptoglobin and alpha2 macroglobulin as fibrosis markers in chronic hepatitis c patients

Hepatitis C virus [HCV] infection is one of the commonest chronic liver diseases worldwide. Progression to chronic disease occurs in the majority of HCV infected patients. The aim of the present work was to study serum levels of alpha2 macroglobulin [alpha2-MG], Apolipoprotein A1 [Apo-1] and Haptoglobin [HP] as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. The study was carried out on 20 patients with chronic HCV and liver cirrhosis [Group I], 20 patients with chronic HCV without liver cirrhosis [Group II] and 10 healthy subjects of mathing age and sex as controls [Group III]. Quantitative estimation of alpha2-MG, HP and Apo AI in serum was done using turbidimetry. The mean serum level of alpha2-MG was significantly higher in group I than in groups II, III [F=12.8] [p=0.00]. On the other hand, Serum Apo A1 and HP were significantly lower in group I than in groups II, III [F=5.9 and 26.3] [p=0.005 and 0.00]. On the other hand, no significant difference was found between groups II and III. Significant positive correlation was observed between serum alpha2-macroglobulin and Child Pugh score, Grading and staging of liver pathology [P<0.05]. On the other hand, significant negative correlation was noticed between serum Apo-1, HP and Child Pugh score, histopathological grading and staging [P<0.05]. Elevated serum levels of alpha2 macroglobulin in addition to low levels of apolipoprotein A1 and haptoglobin might be considered as valuable non invasive parameters for predicting the occurrence of cirrhosis in chronic hepatitis C patients

Gender differences in acute cadmium-induced systemic inflammation in rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes.</p><p><b>METHODS</b>Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) and of major rat acute phase protein alpha 2-macroglobulin (alpha2-M), as soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation.</p><p><b>RESULTS</b>Differential increases of IL-6 and alpha2-M (higher in males than in females) in peripheral blood cell counts and types (leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females) and in levels of neutrophil priming (higher in males vs females) were noted.</p><p><b>CONCLUSION</b>The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.</p>

Non-invasive fibrosis seromarkers as a predictor of liver fibrosis in chronic hepatitis C and/or non-alcoholic steatohepatitis

In patients with chronic hepatitis C, the precise stage of hepatic fibrosis is the most important predictor of disease progression and it determines the need for antiviral therapy. Although liver biopsy is acknowledged as the gold standard for evaluating fibrosis, it is occasionally prone to sampling error and complications. We aimed to correlate an index of biochemical markers with histological features of fibrosis to predict hepatic fibrosis in patients with chronic hepatitis C virus, patients with combined hepatitis C virus and non-alcoholic steatohepatitis and those with non-alcoholic steatohepatitis, aiming to reduce the use of the liver biopsy. Out of those attending our out patient clinic for clinical, haematological, biochemical, virological, histological and ultrasonographic assessment prior to interferon therapy for hepatitis C virus, we enrolled 41 patients and grouped them according to histopathological examination of their liver biopsies into: Group I: 21 chronic hepatitis C virus patients as defined by positive 3rd generation ELISA; Group II: 20 patients with combined hepatitis C virus and NASH. We added a third group [Group III] of 15 patients having non alcoholic steatohepatitis as defined clinically, biochemically and through diagnostic percutanous liver biopsy. There were 33 male 23 female patients; 35 [62.5%] of them were from rural areas and 21 [37.5%] were from urban areas; the mean ages were 40.5 +/- 9, 46.6 +/- 7.7 and 42.13 +/- 11.06 in Group I, II and III respectively. Twenty apparently healthy individuals served as the control group. All the patients and the control group were submitted to full clinical history and examination, abdominal ultrasonography, CBC, liver biochemical profile and fibrosis biomarkers [apolipoprotein A1, haptoglobin, alpha2 marcoglobulin, GGT]. Liver biopsy was done for suitable patients after taking a consent and the results of fibrosis seromarkers were compared with the results of liver biopsy using the Metavir scoring system, We also estimated patients' body mass index, fasting and post prandial blood glucose. We excluded patients with other causes of chronic liver disease and co-morbidities that could confound the results of the non-invasive markers adopted, including schistosomiasis which was excluded by serological test. 43% of Group I and 40% of Group II had advanced fibrosis. None of Group III had advanced fibrosis; mild fibrosis was detected in 80% of them. gamma-GT was found positively correlated to the degree of hepatic fibrosis in Groups I, II and III [r = 0.667, 0.656 and 0.121, respectively] with P values of 0.001, 0.002, 0.668, respectively. alpha2 macroglobulin was found to be a reliable predictor of fibrosis [r = 0.30, P = 0.02] with ROC curve [area under the curve = 0.70] best cutoff value 2.55 g/L with sensitivity of 0.80 and specificity of 0.50. The results of haptoglobin were negatively related to the degree of hepatic fibrosis in Group I and II with ROC curve area under the curve of 0.33 and P value of 0.04. Significant direct correlation was seen in Group III [r = 0.55, P = 0.03], so by regression analysis, haptoglobin can be used as a good predictor for fibrosis in Group III [r = 0.54, P=0.04]. Apolipoprotein A1 has negative correlation to the stage of fibrosis in Groups I and II although the results were statistically insignificant. APRI index was found significantly directly correlated to the fibrosis stage and the grade of inflammation of all studied groups [r= 0.57, P< 0.01 and r = 0.36, P< 0.01, respectively] with a best cutoff value of 0.62, with sensitivity of 0.86 and specificity of 0.57. In patients with advanced fibrosis the best cutoff value was found to be 0.72 with sensitivity of 0.94 and specificity of 0.67. Mordified APRI test showed AUC of 0.79 [P<0.01] with a best cutoff value of 0.067 at which sensitivity and specificity were 0.82 and 0.61, respectively. Alpha macroglobulin, haptoglobin, apolipoprotein A1, APRI index and a modified APRI index, were found be significant predictors of hepatic fibrosis and were reprocessed by stepwise logistic regression

Evaluation of fibrosis sero-markers versus liver biopsy in Egyptian patients with hepatitis C and/or NASH and/or schistosomiasis

Although liver biopsy is acknowledged as the gold standard for evaluating fibrosis, it is occasionally prone to sampling error and complications. Is to correlate an index of biochemical markers with histological features of fibrosis in patients with chronic hepatitis C virus [HCV] and/or non alcoholic steatohepatitis [NASH] with or without schistosomiasis in order to reduce the use of liver biopsy. Fifty-six patients [n-56] attending tropical medicine clinics in Kasr El-Aini and Beni Suef Faculty of Medicine were enrolled and classified into 3 groups according to the histopathological findings of their liver biopsy. Stool and urine analysis were done to exclude passage of Schistosoma ova, in addition to liver biopsy, abdominal ultrasonography, and testing of their sera for fibrosis biomarkers [Apolipoprotein Al, Haptoglobin, Alpha-2-Macroglobulin, and Ganima-glutamyl transpeptidase [GGT]]. Patients with history of contact with canal water [35 patients] were screened for Schistosoma mansoni infection by detecting anti-Schistosoma IgG antibodies and circulating Schistosoma soluble egg antigen using indirect ELISA and sandwich ELISA techniques, respectively. Forty-three [43%] of group I [HCV] and 40% of group II [HCV and NASH] had advanced fibrosis [F3 and F4]. Out of the 35 patients with positive history of canal water contact 25 [71.4%] were antibody positive; Schistosoma antigen was detected in only 5 patients [14.3%], with no statistically significant differences in the level of fibrosis seromarkers from other patients. Alpha-2-macroglobulin was found to be a reliable predictor of fibrosis. Haptoglobin was negatively related to the degree of hepatic fibrosis in groups I and II and significantly directly correlated in group III [NASH]. By regression analysis, haptoglobin can be a good predictor for fibrosis in group Ill. Apolipoprotein Al had insignificant negative correlation to the stage of fibrosis in groups I and II. GGT was positively correlated to the degree of hepatic fibrosis in groups I, II and III. AST/platelet ratio index [APRI] proved significantly directly correlated with fibrosis stage and grade of inflammation of the studied patients. Co-infection with schistosomiasis in patients with HCV and/or NASH gave no statistically significant differenceinfibrosis staging in all groups.Alpha-2-macroglobulin, haptoglobin and apolipoprotein Al, besides APRI index and modified APRI index proved to be significant predictors of hepatic fibrosis

Effects of tobacco smoking on alpha-2-macroglobulin and some biochemical parameters in Thai males.

This cross-sectional study was carried out among smokers and nonsmokers from suburban and urban residential areas in Bangkok, Thailand. One hundred eighty-six smokers and 102 nonsmokers, who voluntarily participated in the study, were investigated. The levels of alpha-2-macroglobulin (A2M), albumin, total protein, and other biochemical and hematological parameters as well as body mass index (BMI) measurements were taken. The levels of A2M, BUN and WBC counts were significantly higher in smokers than nonsmokers. Total protein and albumin concentrations were significantly lower in smokers than nonsmokers, but the levels of other biochemical parameters did not differ between the two groups. The relationship between BMI and median A2M levels in the smoker and nonsmoker groups showed the higher the BMI, the lower the serum A2M levels. Smokers had a higher percentage of hyperalpha-2-macroglobulinemia than nonsmokers. A2M concentrations correlated inversely with BMI, BUN, albumin, total cholesterol, triglycerides, and the quantity of cigarettes smoked for the total period of smoking (cigarette pack-years). Multiple regression analysis revealed that albumin and cigarette pack-years were the most closely related variables to A2M concentrations among smokers. These findings suggest cigarette smoking affects inflammation markers, increasing A2M and WBC and decreasing albumin. This effect may be the mechanism responsible for the development of chronic disease states associated with smoking since cigarette smoke contains many toxic compounds harmful to health.

Alpha 2 macroglobulin activity in rats infected with Typanosoma lewisi and treated with cyclophosphamide and its effect on the malignancy of the disease.

BACKGROUND & OBJECTIVES: Trypanosoma lewisi is a common, flagellated parasite of the rat. Our previous study showed that rabbits injected with serum collected from rats infected with Trypanosoma lewisi and treated with cyclophosphamide (CyI) produced high levels of antibodies against a new protein in the CyI rat serum. RESULTS: In the present study, this protein was characterised as alpha2 macroglobulin (alpha2M) and the kinetics of its production and its influence on the malignancy of the disease were determined. In rats infected with T. lewisi, alpha2M was first demonstrated and peaked on the second day post-infection (972 microg/ml) and then reduced gradually, reaching a level of 32 microg/ml on the eighth day post-infection. However, in the CyI rats the level of alpha2M was gradually increased as the disease progressed, reaching a level of 890 microg/ml on the eighth day post-infection. Injection of both crude and purified alpha2M into rats infected with T. lewisi led to increased parasitaemia. INTERPRETATION & CONCLUSION: The present study suggests that increased levels of alpha2M in the CyI rats contribute to the malignancy of the disease.

Role of hepatocyte growth factor, vasointestinal peptide, angiotensine ii and alpha 2-macroglobulin in male fertility

The aim of this work is to assess the prognostic validity of some seminal plasma parameters in male infertility and spermatogenesis; such as Hepatocyte Growth Factor [HGF], Vasoactive intestinal Peptide [VIP], Angiotensin II, Alpha-2 Macroglobulin, Total proteins, Albumin, Globulin and Albumin /Globulin ratio. In the current study, 105 infertile cases of different categories according to their semen analysis were compared to 15 normozoospermic fertile cases. The infertile case were divided into; OAT with and without varicocele, AT with and without varicocele, obstructive azoospermia and NOA [TESE +ve and TESE -ve]. Azoospermic cases were subjected to testicular biopsy for both histopathology and diagnostic TESE. Seminal plasma ELISA estimation of hepatocyte growth factor, vasoactive intestinal peptide, angiotensin II, alpha-2 macro-globulin. Seminal plasma total proteins, albumin, globulin were estimated calorimetrically. Seminal plasma testicular contribution was evident in all tested factors except hepatocyte growth factor [VIP 56.4%, AT II 64.1%, alpha-2 M 57.7%, total protein 41.1%, albumin 41% and globulin 42.9%]. Varicocele affects adversely with significance the contribution of different studied parameters in seminal plasma. Also there was significant reduction in the testicular size in left sided varicocele. SP A/G ratio and alpha-2 macroglobulin can differentiate between TESE+ and TESE-. Otherwise, other factors have poor ability. SP HGF, VIP, ATII and alpha-2 M can confirm differentiating OA and NOA. There was negative significant correlation between abnormal form percentage and sperm motility percentage. There was significant positive correlation between SP total protein and sperm concentration in OAT- group and between SP globulin and sperm motility percentage in AT- group. Albumin has no correlation with seminal sperm parameters, in all groups except positive significant correlation with abnormal form percent in AT+. There was positive significant correlation between alpha2-M and total proteins in all studied groups. SP factors appear to act in coordination and harmony more than individually or separately

Association of the polymorphism in alpha-2 macroglobulin gene with essential tremor and Parkinson's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the association of two polymorphisms of alpha-2 macroglobulin gene (A2M), a 1000G/A in exon 24 and a pentanucleotide insertion/deletion (I/D) in the 5'splice site in exon 18, with Parkinson's disease (PD) and essential tremor (ET) in North China.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to investigate 87 cases of Parkinson's disease (PD),73 cases of ET and 100 randomly selected healthy control subjects.</p><p><b>RESULTS</b>(1) The allelic and genotypic distributions of A2M G/A were significantly different among the PD, ET patients and controls (P<0.05). The allele G and genotype GA in PD patients were significantly higher than those in ET patients or controls (P<0.05). There was no statistically significant difference between ET patients and controls in allelic and genotypic distribution (P>0.05). (2) The differences in allelic and genotypic distributions of A2M I/D among PD, ET patients and selected controls were found to be of no statistical significance (P>0.05).</p><p><b>CONCLUSION</b>(1) The polymorphism at the site of G/A might be associated with PD, but there might be no genetic association of polymorphism at this site with ET. (2) There might be no association of polymorphism at the site of I/D with PD and ET in North China.</p>

No evidence for genetic association between alpha-2 macroglobulin I1000V polymorphism and sporadic Alzheimer's disease in two independent Chinese populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Alpha-2 macroglobulin (alpha2M) is a proteinase inhibitor found in association with senile plaques in Alzheimer's disease (AD). Also alpha2M has been implicated in several pathophysiological processes in AD. In view of the recent contradictory reports on the relationship between AD and a common polymorphism I1000V in A2M gene, the present authors studied a relatively large sample, determined the genotype of the I1000V polymorphism in A2M gene in sporadic AD patients and age-matched controls with normal cognition, and examined the possible association of the polymorphism with AD.</p><p><b>METHODS</b>Genotypes of A2M and apolipoprotein E (apoE) were detected by polymerase chain reaction combined with restriction fragment length polymorphism in 257 patients and 242 controls in Guangzhou, and 112 patients and 113 controls in Chengdu.</p><p><b>RESULTS</b>The 1000Val allele frequencies in the merged AD and control groups were 7.7% and 8.7%, respectively. The differences of allelic and genotypic frequencies between the patients and control subjects were not statistically significant, even after stratification by apoE epsilon4 status or by age-of-onset of the disease.</p><p><b>CONCLUSION</b>The results of this study revealed no association between the I1000V polymorphism of A2M and Chinese sporadic AD in Guangzhou and Chengdu.</p>

Fisiopatologia da fibrose cardíaca chagásica: papel de TGF-Beta / Physiopathology of fibrosis chagasic cardiac: TGF-Beta paper

A miocardiopatia crônica é uma das principais manifestações associadas à morbidade na doença de Chagas, sendo possivelmente desencadeada pelas interações parasita-hospedeiro durante a fase aguda.A fibrose é uma das manifestações mais significativas da cardiopatia chagásica crônica e encontra-se associada com infiltrados inflamatórios e cardiomiócitos em degeneração.O TGF-beta é uma das principais citocinas envolvidas na regulação da formação e degradação de matriz extracelular e,portanto, dos processos fibróticos.Neste trabalho focalizamos nossa atenção no possível papel do TGF-beta como agente indutor/regulador de manifestações da cardiopatia chagásica,especialmente a fibrose.Estudos realizados com pacientes cardiopatas chagásicos crônicos,nos apontam para uma relação de TGF-beta com o desenvolvimento da fibrose.Nossos resultados demonstram...também apresentavam intensa fibrose e alta atividade biológica de TGF-beta no coração.Além disso,descrevemos que células miocárdicas de pacientes ou de modelos experimentais submetidos aos efeitos de níveis elevados de TGF-beta sofrem alterações no padrão de distribuição de Cx43 que podem estar relacionadas ao comprometimento da condutividade elétrica no coração e conseqüente arritmia.Como o TGF-beta já havia sido descrito como molécula mediadora dos processos de invasão celular na infecção pelo T.cruzi,estudamos a capacidade deste parasita em ativar e captar o TGF-beta do hospedeiro.Observamos que o T.cruzi é capaz de ativar TGF-beta latente de forma dose-e temperatura-dependente. Esta capacidade de ativação de TGF-beta era observada pela presença direta de parasitas vivos e de seus extratos total e citosólico,por um fator possivelmente protéico ou lipídico.Além disso,observamos que formas amastigotas de T.cruzi captam e internalizam TGF-beta do hospedeiro,estocando-o,para liberação no momento da diferenciação para tripomastigotas,o que evidencia um novo papel de TGF-beta no ciclo celular do parasita.O TGF-beta poderia estar sendo usado pelo parasita no momento de sinalizar a parada de proliferação e a diferenciação para tripomastigotas.Num contexto geral,a capacidade de T.cruzi para estocar e ativar TGF-beta poderia estar relacionada com diversos mecanismos diretos e indiretos atuantes no desenvolvimento da doença de Chagas.A manutenção de TGF-beta no tecido cardíaco pode estar diretamente relacionada com a formação de fibrose e com arritmias,além de sustentar a manutenção de uma carga residual de parasitas.

Correlation between biochemical markers of liver fibrosis and histopathological features in patients with chronic hepatitis C

Aim: Liver fibrosis in chronic hepatitis C is related to sex and age at infection. Several biochemical markers are highly predictive for the discrimination of significant fibrosis. The aims of this study were to compare an index of five-biochemical markers with histological features and to determine the utility of combining historical features [age and sex] with the five-marker index for the prediction of significant fibrosis. Subjects and Thirty untreated patients with chronic hepatitis C and a known duration of infection had a liver biopsy and serum tested for markers of fibrosis. The discriminative values of the markers and an index of historical features for the diagnosis of clinically significant fibrosis [F2-F4, by the Metavir scoring system] were compared using areas under receiving operating characteristic [ROC] curves. A modified index was constructed combining the five-marker index and historical features. Of the 30 patients included 70% were males. The median age at infection was 28 +/- 13 and the median duration of infection was 17 +/- 8 years. By multivariate logistic regression analysis, sex [P=0.003], age at biopsy [P-0.004] were independently predictive of F2-F4 fibrosis. For the discrimination of F2-F4 fibrosis, the areas under ROC curves were 0.796 +/- 0.033 for the five-marker index versus 0.709 +/- 0.037 for the historical index [P=0.079]. For diagnosis of advanced fibrosis [F3, F4] the areas under the curves were 0.920 +/- 0.032 and 0.762'0.049 [P=0.007], respectively. The discriminative value of the combined biochemical and historical index was not statistically significantly different from that of the five-marker index alone [P=ns]. Conclusions: A simple index including age, sex, and five biochemical markers accurately predicts significant hepatitis C related fibrosis

Role of decisive markers in diagnosis and outcome of patients with septic shock

This work aimed to assess the potential role of procalcitonin [PCT] and polymorphonuclear [PMN] elastase enzyme in the early diagnosis and early prediction of prognosis in patients with sepsis and septic shock. Twenty patients with septic shock [16 males and 4 females, mean age 50.15 years] together with a second group comprising 10 patients [9 males, mean age 49.2 years] with systemic sepsis without shock were studied. A third group including 20 healthy volunteers matching with age and sex and served as controls. Serum PCT and PMN elastase enzyme levels were estimated on admission for both patients and control groups with other laboratory investigations and clinical parameters. A multivariate discriminate analysis was performed using PCT, PMN elastase enzyme, albumin, alpha-1-antitrypsin, alpha-2 macroglobulin and C-reactive protein [CRP] as independent parameters. The study concluded that serum PCT and PMN elastase enzyme are independent useful diagnostic markers for the early detection of systemic inflammatory response syndrome with or without shock. However, PCT has the advantage over the above mentioned parameters having significantly predictive accuracy of 80%. Procalcitonin, PMN elastase enzyme, alpha-1-antitrypsin, alpha-2-macroglobulin, CRP and albumin could be used for the early prediction of complications of sepsis patients with an overall predictive accuracy of 76.7%

Study on certain serum glycosylated proteins and lipids in diabetic retinopathy

The aim of the present work was to through more light on some factors involved in the vascular complications in diabetes mellitus; namely, plasma fibronectin and plasma alpha-2-macroglobulin in diabetics with normal fundus and in diabetics with retinopathy in a trial to clarify their possible role. Fifty diabetic patients [30 with retinopathy and 20 without retinopathy], in addition to 20 healthy control subjects were included in the present study. The study concluded that alpha-2-macroglobulin is a valuable indicator in the development of angiography in general than fibronectin, since the former was proved to be significantly elevated in diabetics with retinopathy than without, in addition to its significant correlation with microalbuminuria. Fibronectin showed neither elevation in retinopathic diabetics nor any correlation with microalbuminuria

Apolipoprotein E Gene and Alpha 1-Antichymotrypsin Gene in Brain of Sporadic Alzheimer's Disease

BACKGROUND: This study aims to detect any causative genetic alterations and to demonstrate any correlations of these genes in the pathogenesis of mostly late-occurring sporadic type of Alzheimer's disease (AD). METHODS: A total of 67 registered cases of autopsy-confirmed brain tissues were analyzed. Included here was sporadic AD (n=41), vascular dementia (n=17), and non-demented physiologically aging control brains (n=9). ApoE genotyping was done with the enzymatic digestion, and allele specific PCR was done to analyze the -491 A/T polymorphism of ApoE. Detection of polymorphism of alpha 2-macroglobulin (A2M) was done with enzymatic digestion and DNA sequencing. RT-PCR products were electrophoresed to detect mRNA expression of alpha 1-antichymotrypsin (ACT). RESULTS: A prevalence rate of ApoE E4 genotype (E3/E4, E4/E4) showed significantly higher in patients with AD than in patients with vascular dementia (43.8% vs. 11.7%, p=0.019). Only 1 out of 4 cases of sporadic AD was associated with the E4/E4 allele. -491A/ T polymorphism of the ApoE promoter was found only in AD (2/41 cases, 4.9%). The incidence of heterozygous allelic polymorphism with 5 bp deletions in exon 18 of A2M-2 was 4.9% (2 out of 41) in AD. Messenger RNA expression of ACT, which is closely associated with the ApoE E4 allele, was increased in AD in comparison with normal control (p=0.0002). CONCLUSIONS: ApoE4 genotype and ACT are closely related to the pathogenesis of late-onset sporadic AD. Neither -491 polymorphism of ApoE promoter nor A2M-2 showed close association with AD in these brain samples.

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.