Serum butyrylcholinesterase activities in patients with non-alcoholic fatty liver disease. Comparison with liver proteosynthetic function and liver fibrosis.

BACKGROUND: We aimed to determine how does butyrylcholinesterase (BChE) activity change in the serum of NAFLD patients, whether there was a relationship between BChE and the severity of NAFLD and whether BChE could be used to distinguish the patients with simple hepatic steatosis from the patients with non-alcoholic steatohepatitis. METHODS: The study group consisted of 64 patients with NAFLD. Patients were examined for fatty liver index and in the serum, we investigated BChE activities and the concentrations of prealbumin, cholesterol, HDL-cholesterol, triacylglycerols and hyaluronic acid (HA). We also used FIB-4 index to evaluate liver fibrosis. RESULTS: BChE activity was significantly increased in NAFLD patients compared to the controls (4711 U/l vs 4028 U/l). Patients with higher concentrations of serum triacylglycerols and non-HDL cholesterol had also significantly higher activities of BChE. The comparison of BChE activity and parameters of liver fibrosis (HA and FIB-4) showed a significant negative correlation between these parameters. Patients with an increased concentration of HA had significantly lower BChE than the controls (3111 U/l vs 4028 U/l). CONCLUSIONS: Our results showed increased BChE values in NAFLD patients. The comparison of changes in BChE activity with the changes in prealbumin levels and changes of both fibro markers showed that the examination of BChE activity could help to differentiate NAFLD patients with a simple hepatic steatosis from those with an advanced disease (Tab. 1, Fig. 7, Ref. 28). Text in PDF www.elis.sk Keywords: butyrylcholinesterase, non-alcoholic fatty liver disease, hyaluronic acid, FIB-4, fatty liver index.

Central systolic blood pressure (cSBP) to brachial systolic blood pressure (brachSBP) ratio reproducibility during antihypertensive therapy.

OBJECTIVES: Higher CSBP than brachial SBP in individual patient increases cardiovascular (CV) risk. For follow-up it is important to assess the reproducibility of such measurements. The aim of this study was to assess the reproducibility of these differences, expressed as a CSBP/BrachSBP ratios. SUBJECTS AND METHODS: Eighty-three patients on antihypertensive therapy were analysed for the reproducibility of such ratios after time interval of several month up to several years. For CSBP estimation, we used the Arteriograph (Tensiomed Ltd.), based on blood pressure measurements by cuff on oscillometric principle, using pulse wave analysis (PWA) for assessment of CSBP. RESULTS: The proportion of patients retained the same characteristics (either higher central or higher peripheral SBP) between the first and second measurement was 71.1 %. The association between 1st and 2nd measurement, was statistically significant, p < 0.001. CONCLUSION: In our study, a high proportion (60 %) of treated hypertensive patients had CSBP higher than brachial SBP, which may adversely influence their prognosis. This characteristic is highly reproducible. Taking into the account these differences may increase the exactness of CV risk estimation and may contribute to explanation of residual risk of individual patient (Tab. 3, Fig. 1, Ref. 28).

Central systolic blood pressure increases with aortic stiffness.

OBJECTIVES: Central systolic blood pressure (CSBP) is the pressure in the root of aorta, which directly influences organs such as brain, heart and kidneys and is related to organ damage. Its value increases with the aortic stiffness. The aim of this study was to analyze the relationships of CSBP to aortic stiffness parameters. METHODS: Central blood pressure (BP) and related parameters were measured by Arteriograph, working based on oscillometric principle, using pulse wave analysis (PWA) approach. We examined 123 patients (69 females, 54 males) with a primary hypertension. RESULTS: Using a linear correlation analysis, we found that CSBP was correlated to aortic pulse wave velocity (PWV), aortic and brachial pulse pressure (PP), aortic augmentation index, return time of reflected pressure wave (RT) and aortic and brachial augmentation indexes. Multivariate analysis defines the aortic pulse pressure (PPao) as the most powerful parameter influencing CSBP. By an individual analysis of BP in each patient separately, we defined two different types of central hemodynamics; those with a higher CSBP than brachial SBP occur in stiffer aorta. CONCLUSION: The CSBP increases with aortic PP, the most powerful stiffness parameter of aorta. Higher CSBP than brachial SBP usually accompanies a stiffer aorta (Tab. 5, Ref. 19).

Can alpha-1-acid glycoprotein affect the outcome of treatment in a cancer patient?

Alpha-1-acid glycoprotein (AGP) is a glycoprotein found in the alpha-1 globulin fraction of human plasma proteins. AGP is an important representative of acute-phase proteins. Although numerous articles have been devoted to AGP, its exact biological function remains obscure. AGP levels increase with a number of diseases. One of them is a tumor disease. In our paper, we discuss the role of increased AGP levels in cancer patients. We deal with the role of AGP as a drug-binding protein and its effect on the efficacy of chemotherapy in oncological patients. Other problems that are discussed in our paper include the role of AGP as an immunomodulatory protein and its relationship to angiogenesis because angiogenesis plays an important role in the progression of cancer (Ref. 57). Keywords: alpha-1-acid glycoprotein, orosomucoid, cancer, disease marker, immunomodulatory protein,drug-binding protein.

Alpha-2-macroglobulin and hyaluronic acid as fibromarkers in patients with chronic hepatitis C.

BACKGROUND: Liver fibrosis is the final common pathway of chronic liver diseases of various etiology. From the practical standpoint, it would be ideal to have a noninvasive fibromarker. The aim of our study was to investigate the levels of alpha-2-macroglobulin, potential fibromarker, in correlation to histological staging and another potential fibromarker, hyaluronic acid, in patients with chronic hepatitis C. METHODS: Population groups in this study consisted of 51 healthy volunteers and 54 patients with chronic hepatitis C. Liver biopsies were obtained under ultrasound guidance. Alpha-2-macroglobulin was determined by electroimmunodiffusion and hyaluronic acid with enzyme-linked binding protein assay. RESULTS: Both potential fibromarkers, alpha-2-macroglobulin and hyaluronic acid, were increased in patients with chronic hepatitis C. The alpha-2-macroglobulin levels were not significantly increased in the groups F0-F1. In the groups F2-F4, alpha-2-macroglobulin levels were significantly higher than in the control group. The changes of hyaluronic acid were similar to changes of alpha-2-macroglobulin. Regression analysis showed a significant correlation between hyaluronic acid and alpha-2-macroglobulin levels. CONCLUSIONS: According to the results of our study, it can be concluded that alpha-2-macroglobulin and hyaluronic acid might be useful markers of liver fibrosis (Tab. 2, Ref. 15).

Paraoxonase activity in sera of patients with non-alcoholic fatty liver disease.

The results of our study showed significantly decreased levels of PON1 in patients with chronic liver diseases (controls 185 ± 14 U/l, NAFLD 160 ± 15 U/l, chronic hepatitis 99 ± 18 U/l, cirrhosis 52 ± 11 U/l). There were significant correlations of PON activities with standard liver function tests (Tab. 1, Ref. 5).

Peroxisomal enzymes in the liver of rats with experimental diabetes mellitus type 2.

Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b(5) reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy.

The role of oxidative stress in anti-tumor necrosis factor antibody treatment in Crohn's disease.

Administration of anti-tumor necrosis factor alpha antibodies [anti-TNF]-alpha represents a therapeutic approach aimed to diminish the effects of tumor necrosis factor [TNF]- alpha in Crohn's disease [CD]. Blockade of its action should be related to various changes including those in immune and inflammatory response. There is a growing body of experimental data to suggest that the chronically inflamed intestine may be subjected to considerable oxidative stress. The aim of this study was to study the impact of therapy with anti-TNF [infliximab] on Crohn's disease activity index [CDAI], markers of inflammatory activity and oxidative stress. Fourteen patients with active CD received 5mg/kg of infliximab in a single intravenous infusion. CDAI, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fibrinogen [FBG], alpha-1 antitrypsin [AAT], albumin [ALB], ceruloplasmin apoprotein [CP], ferroxidase activity of CP [FOACP], specific enzymatic activity of CP [SEACP] and conjugated dienes [DIE] were determined before treatment in month 0 [M 0], in 1st control period in month 1 [M 1] and in 2nd control period in month 5 [M 5] after treatment. In clinical activity a sustained significant decrease in CDAI was observed, with a significant drop in M 1, remaining in M 5. A significant decrease in ESR in M 1, accompanied by insignificantly reduced levels of CRP and FBG was present. During the further follow up in M 5 a slight increase of ESR, CRP and FBG was noticed. A significant decrease of AAT in M 1 was present; this decrease was followed by a significant increase in M 5. Ceruloplasmin apoprotein levels dropped in M 1, with further slight insignificant increase in M 5. A significant increase of ALB sustaining in M 5 was present. The levels of DIE slightly decreased in M 1 and significantly in M 5, together with the slight increase of the FOACP and SEACP in M 1 and significant increase in M 5. We conclude, that oxidative stress may be important in the pathogenesis and perpetuation of tissue injury in CD patients. The decreasing levels of DIE together with the increase of the FOCP and SEACP after infliximab treatment together with changes of markers of inflammatory activity, can participate in the improvement of clinical status of patients with CD.

Plasma copper and ceruloplasmin in patients with alcoholic liver steatosis.

BACKGROUND: In blood plasma, copper is transported in form of ceruloplasmin. Ceruloplasmin is not only a simple transport protein, it is a multifunctional protein with other various physiological functions. At least a part of these functions is connected with ceruloplasmin's enzymatic activity. AIM OF THE STUDY: The effect of alcoholic fatty liver on the metabolism of copper and ceruloplasmin was studied. MATERIAL AND METHODS: Patients suffering from alcoholic liver steatosis were enrolled in the study. The serum levels of copper, apoceruloplasmin and oxidase activity of ceruloplasmin were determined. RESULTS: The copper level in patients with liver steatosis was moderately decreased in comparison to healthy controls. The difference in apoceruloplasmin levels between patients with liver steatosis and healthy controls was not significant, but the specific activity of ceruloplasmin in patients was significantly decreased in comparison to controls (0.59 vs. 0.82, p<0.001). The decreased specific activity of ceruloplasmin in spite of normal levels of apoceruloplasmin in patients with alcoholic liver steatosis suggested some problems in copper metabolism in these patients. CONCLUSIONS: The results of our study showed disturbances in copper and ceruloplasmin metabolism in patients with alcoholic liver steatosis. We can conclude that the determination of blood plasma ceruloplasmin level on the basis of its enzymatic activity is better than a simple determination of apoceruloplasmin (Tab. 2, Ref. 14).

[Molecular genetic diagnostics and screening of hereditary hemochromatosis]. / Molekulovo-genetická diagnostika a skríning hereditárnei hemochromatózy.

BACKGROUND: Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. PATIENTS AND METHODS: The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. RESULTS: In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p < 0.001), C282Y/H63D compound heterozygotes (p < 0.05) or wild type subjects (p < 0.001) respectively. Also serum ferritin levels were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p < 0.001), C282Y/H63D compound heterozygotes (p < 0.001) and wild type subjects (p < 0.001) respectively. CONCLUSIONS: Our observations confirm that DNA analysis significantly contributes to differential diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. DNA analysis is recommended in patients whose transferrin saturation is 45% or more on a repeated test. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with secondary iron overload, especially patients with chronic liver disorders and chronic anemia. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified.

Serum magnesium levels in patients with alcoholic and non-alcoholic fatty liver.

INTRODUCTION: Magnesium is currently a subject of major interest in biology and medicine. Magnesium is intimately involved in over 300 enzymatic reactions. particularly in processes involving the formation and utilization of ATP. It is known that alcoholism is connected with hypomagnesemia. There are also several studies describing the disorders of magnesium balance in patients with liver diseases. THE AIM OF STUDY: was to investigate the serum magnesium levels in patients with liver steatosis. We compared the magnesium levels in patients with non-alcoholic and alcoholic fatty liver to estimate if alcoholism is the only cause of magnesium disorders or if also liver function disorders play any role in the development of magnesium dysbalance in patients with liver steatosis. PATIENTS AND METHODS: The studied group consisted of 44 patients with hepatic steatosis (25 non-alcoholic and 19 alcoholic). The control group consisted of 57 healthy subjects. Magnesium levels were assayed by atomic absorption spectrometry. RESULTS: Serum magnesium levels were significantly decreased in patients with alcoholic (0.67 +/- 0.10 vs 1.02 +/- 0.11 mmol.l(-1)) and also in patients with non-alcoholic liver steatosis (0.65 +/- 0.14 vs 1.02 +/- 0.11 mmol.l(-1)). There were also moderately increased activities of aminotransferases and gamma-glutamyltransferase. Plasma triacylglycerols were increased in both studied groups. Albumin and prealbumin levels were not changed in comparison to the control group. There was a slight increase in plasma levels of immunoglobulin A and immunoglobulin G. CONCLUSIONS: The results of our study showed hypomagnesemia in both studied groups. Decreased magnesium levels found also in patients with non-alcoholic fatty liver suggest that alcoholism cannot be the only cause of hypomagnesemia in patients with fatty liver. Hypomagnesemia is not only a laboratory symptom of fatty liver but due to its connection with increased oxidative stress it might be a risk factor in the progression of fatty liver to steatohepatitis (Tab. 3, Ref: 19).

Serum cholinesterase activity and proteosynthetic function of liver in patients with diabetes mellitus.

INTRODUCTION: Diabetes mellitus is associated with a lot of changes in intermediary metabolism and several authors reported on higher frequency of liver diseases in patients with diabetes. AIM OF THE STUDY: Was to establish the changes of blood serum cholinesterase, prealbumin and albumin, parameters which are accepted as an index of liver proteosynthetic function, in patients with diabetes mellitus. PATIENTS AND METHODS: The study group consisted of 207 patients with diabetes mellitus (83 patients with type I and 124 patients with type II diabetes mellitus). Control group consisted of 179 healthy subjects. The activity of cholinesterase was assayed by the kinetic method, concentrations of prealbumin and albumin were determined immunochemically. RESULTS: Activity of serum cholinesterase was significantly higher in group of patients with diabetes mellitus than in control group (65.05 vs 73.33 microkat/l). The concentration of prealbumin was lower in blood serum of patients with diabetes than in controls (308.10 vs 285.85 mg/l). Serum levels of albumin were not different in both studied groups. After dividing of patients according to the type of diabetes, 80 % of abnormal values of cholinesterase and prealbumin were present in patients with type II diabetes. CONCLUSIONS: The results of our study showed abnormal values of determined liver tests approximately in 22 % of patients with diabetes mellitus. The character of laboratory changes--increased activity of cholinesterase, decreased concentration of prealbumin and normal levels of albumin, suggests development of liver steatosis in these patients. The most of pathological findings were in patients with diabetes type II (Tab. 3, Ref. 20).

[Liver biopsy in Slovakia]. / Biopsie pecene na Slovensku.

INTRODUCTION: Liver biopsy is the most specific diagnostic modality in hepatology, but information about its application in Slovakia is rather obscure. METHODS: The authors performed a correspondence study with the aim to find out how many biopsy examinations has been done in Slovakia in 2001, for which indications, what kind of techniques have been applied and which small or great complications were encountered. RESULTS: It was established that in the year 2001, 400 biopsies for diffuse liver diseases were performed. There were 296 percutaneous biopsies, 82 laparoscopic biopsies and 22 trans-jugular biopsies forming the survey. Acute viral hepatitis was the most frequent indication, whereas non-alcohol steatohepatitis was a rare indication in spite of the high prevalence. The frequency of great complications was 0.00025%. No death associated with this procedure was reported. CONCLUSION: Liver biopsy has been done in Slovakia in indications, ways and with the frequency of complications, which were comparable with data from literature.

Changes in acute phase proteins after anti-tumor necrosis factor antibody (infliximab) treatment in patients with Crohn's disease.

Acute phase proteins and markers of proteosynthetic activity reflect the clinical activity in Crohn's disease (CD). The impact of anti-tumor necrosis factor antibody (anti-TNF) therapy on serum levels of acute phase proteins and proteosynthetic markers was studied. Fourteen patients with active CD were treated with 5 mg per kg of anti-TNF in intravenous infusion. Clinical activity (assessed by Crohn's disease activity index - CDAI), alpha-1-acid glycoprotein, haptoglobin, cholinesterase and prealbumin were assessed before and in months 1 and 5 after treatment. A sustained decrease in CDAI was observed. This was accompanied by a significant decrease in alpha-1-acid glycoprotein and haptoglobin in month 1 (p=0.005 and p=0.01, respectively) while in month 5 the levels of both acute phase proteins rose significantly (p=0.003 for alpha-1-acid glycoprotein and p=0.02 for haptoglobin). Cholinesterase and prealbumin significantly increased in month 1 after the treatment (p=0.02 and p=0.0006, respectively), the increase was sustained in cholinesterase while prealbumin levels diminished in month 5. We conclude that the clinical improvement after anti-TNF therapy for CD is accompanied by changes of acute phase proteins and proteosynthetic markers. The assessment of these laboratory markers may be useful in the management of CD patients treated with anti-TNF.

Different patterns of serum interleukin 10 response to treatment with anti-tumor necrosis factor alpha antibody (infliximab) in Crohn's disease.

Administration of anti-tumor necrosis factor antibody (anti-TNF, infliximab) down-regulates T helper 1 (Th 1) cytokines production in intestinal mucosa of patients with Crohn's disease (CD). Interleukin 10 (IL-10) is thought to be involved in CD pathogenesis through regulation of the Th 1 response. The aim of this study was to determine the IL-10 response in CD patients treated with anti-TNF. Fourteen patients with active CD received 5 mg/kg of infliximab; clinical activity assessed by Crohn's Disease Activity Index (CDAI), alpha1-acid glycoprotein and serum IL-10 were determined before and after treatment, in month 0, 1 and 5. In the group with a good clinical response, IL-10 levels diminished significantly in month 1 (p<0.05) and remained decreased in month 5. The group with a lower response showed a significant increase in IL-10 levels in month 1 (p<0.05). alpha1-acid glycoprotein levels obtained before treatment were significantly elevated in the group with a good clinical response (p<0.05) and a significant decrease in month 1 was observed in this group (p<0.05). These observations suggest that a pattern of IL-10 response might be related to the clinical response to anti-TNF treatment in CD.

Plasma lipid parameters in patients with alcoholic fatty liver after treatment with essential phospholipids.

BACKGROUND: Fatty liver is the earliest and most common response to alcohol. The accumulation of lipid particles in hepatocytes alters the ultrastructure of cellular membranes. The purpose of our study was to investigate the effect of the administration of essential phospholipids on plasma lipid parameters in patients with alcoholic fatty liver. METHODS: Our open clinical trial was performed in patients suffering from alcoholic fatty liver. The investigated group consisted of 29 patients. Two capsules of Essentiale forte were administered 3 times daily for 3 months. Individual biochemical parameters were examined each month. Values of total cholesterol, HDL- and LDL-cholesterol, triacylglycerols, apoprotein A and B were determined. RESULTS: The therapy with essential phospholipids had positive effects on the parameters of hepatocyte integrity. The levels of total cholesterol, triacylglycerols and apoprotein B were significantly higher in patients with fatty liver than in the controls. The concentration of HDL-cholesterol was also higher before the therapy than in the control group. There was no difference in levels of apoprotein A and LDL-cholesterol between the patients and the controls. There was no significant therapeutic effect on plasma lipid parameters in the group of patients with fatty liver. CONCLUSIONS: The effects of treatment of alcoholic fatty liver with essential phospholipids were studied. The therapy had positive effects on the parameters of hepatocyte integrity. There was no significant therapeutic effect of the therapy on plasma lipid parameters. (Tab. 2, Fig. 1, Ref. 20).

[Molecular analysis of Wilson disease]. / Molekulární analýza Wilsonovy choroby.

BACKGROUND: Wilson disease is an autosomal recessive disorder, characterized by cooper accumulation and intoxication of the organism. Molecular basis of the disease represent mutations in the gene for the copper-transporting ATPase (ATP7B). METHODS AND RESULTS: The submitted paper deals with results of molecular-genetic examination in 130 unrelated families in which Wilson disease was diagnosed. By denaturing gradient gel electrophoresis (DGGE), the exons with abnormal sequences were detected. Followed by sequencing, 17 causal mutations and 9 silent polymorphism were found. Five novel mutations were detected. After analysis of 260 mutant alleles, 214 (82.3%) were identified. The most frequent mutation, H1069Q, occurred in our population with the frequency of 65.8%. Incidence of other mutations, however, did not exceed 5%. CONCLUSIONS: DNA analysis of the Wilson disease offers prompt and reliable results in affected families. It can help to identify asymptomatic and heterozygote siblings at genetic counselling.

[Monoethylglycinexylidide--a metabolite of lidocaine--as an index of liver function in chronic hepatic parenchymal diseases]. / Monoetylglycínxylidid--metabolit lidokaínu--ako index funkcie pecene pri chronických ochoreniach pecenového parenchýmu.

The changes of biotransformation enzyme system (b.e.s.) activity and capacity in liver diseases significantly influence the metabolism of various xenobiotics. Lidocaine is metabolised through oxidative N-deethylation by b.e.s. resulting in the production of monoethylglycinexylide (MEGX). The aim of this study was the determination of serum MEGX concentration as a model substance for indirect evaluation of liver b.e.s. function in patients with liver steatofibrosis and cirrhosis and the assessment of the possibilities to use it as a quantitave test of liver functional state. The study group consisted of 53 patients, 36 of them with liver disease of different etiology (postviral, ethyltoxic, cryptogenic, liver cirrhosis on the basis of autoimmune hepatitis, liver cirrhosis induced by primary sclerosing cholangitis, primary biliary cirrhosis in the stage of cirrhosis, Wilson's disease in the stage of cirrhosis), 7 patients with liver steatofibrosis and 10 control persons. After intravenous administration of lidocaine (1 mg/kg of body weight), concentration of MEGX was assessed by fluorescence polarization immunoassay (FPIA) using Tdx system in venous blood. The concentration was assesed prior to administration of lidocaine and 15 and 30 minutes after. In the group of liver steatofibrosis the concentrations in the 15th minute after administration were lower comparing to controls, in the 30th minute the difference was less significant. The values of MEGX in cirrhosis group were significantly decreased 15 and 30 minutes after lidocaine administration in comparison with control group. The cirrhosis group was divided into two subgroups: compensated (Ci c) and decompensated (Ci d) and independently of this division into three parts according to score system of Child-Pugh classification (Ci A, Ci B, Ci C). The concentrations 15 and 30 minutes after lidocaine administration in patients with Ci c and Ci d were significantly different, similarly there were statistically significant differences among Ci A, Ci B and Ci C. Statistically significant differences were also between the group of steatofibrosis and whole group of cirrhosis. The concentration of MEGX 15 and 30 minutes after lidocaine administration correlated significantly with the values of albumin, prothrombin time, cholinesterase, Child-Plugh score and bilirubin. MEGX test represents an appropriate and rapid method for the determination of functional liver capacity in patients with liver cirrhosis and liver steatofibrosis, not yet used in Slovak republic. It is a noninvasive test, low time consuming, and when repeated it may provide prognostic information about further development of the disease. MEGX test is an appropriate index of liver function and may contribute to early treatment of chronic liver diseases. (Tab. 9, Fig. 10, Ref. 47.)

[Alpha 2-macroglobulin in the blood of patients with diabetes mellitus]. / Alfa2-makroglobulín v sére pacientov s diabetes mellitus.

Human alpha 2-macroglobulin, a plasma glycoprotein, traps and inhibits proteolytic enzymes which participate in inflammation and homeostasis. There is no doubt about the significant role of alpha 2-macroglobulin in immunoregulatory processes. The aim of the present study was to investigate the levels of alpha 2-macroglobulin in patients with diabetes mellitus and to investigate whether an association exists between alpha 2-macroglobulin level and the type of diabetes (type I or type II) or alpha 2-macroglobulin and diabetic complications. The patient population consisted of 48 patients with diabetes mellitus type I (average age 36.5 years) and 50 patients with diabetes type II (average age 55.3 years). Patients were divided into three groups according to the presence of complications (group I--patients without complications, group II--patients with diabetic retinopathy, group III--patients with several complications). alpha 2-macroglobulin was determined by electroimmunoassay according to Laurell. alpha 2-macroglobulin levels were significantly raised in group of diabetics type I (3190 mg/l vs. 1880 mg/l). In the group of diabetics type II alpha 2-macroglobulin levels are within the normal range (2030 mg/l vs. 1880 mg/l). After dividing of diabetics according to the presence of diabetic complications, alpha 2-macroglobulin levels in patients with diabetic complications were significantly higher than in the group of diabetics without complications (3180 mg/l vs. 2040 mg/l). The possible explanations of elevated alpha 2-macroglobulin levels in diabetics and possible participation of elevated a2-macroglobulin in the development of diabetic angiopathy are discussed. (Fig. 2, Ref. 14.)

[Biochemical markers of fibrogenesis in liver diseases]. / Biochemické markery fibrogenézy pri pecenových ochoreniach.

Chronic liver disease evaluation is a very complicated process requiring complex assessment of numerous liver functions. In addition to standard methods of investigation we perform biotransformation liver tests for evaluation of microsome enzyme system. Markers of fibrogenesis represent modern noninvasive tests for fibrotic liver process detection in different diseases. The key role in the process of fibrogenesis have the adipose liver cells (ITO cells) producing collagen I, III, IV and lamilin. These cells may be transformed into myofibroblasts-like cells under specific conditions. Kupffer cells and monocytes produce substances stimulating the proliferation and transformation of liver ITO cells as also proteoglycans and hyaluronic acid synthesis. Mediators of this fibrogenetic activity are platelet derived growth factor (PDGF), transforming growth factors alpha and beta, lymphokines and monokines released by T-lymphocytes and macrophages, interleukin 1-alpha and interferon-tau. Acetaldehyde and its metabolites are important stimulators of collagen production by liver fibroblasts. The most often used markers of hepatic fibrogenesis are the following: procollagen III peptide, procollagen IV. type (one of its end carboxypeptide chains is determined-either with 7s collagen or NC1), hyaluronic acid, fibronectin, tenascine and unduline. As the most sensitive markers of fibrinogenesis are considered: hyaluronic acid, laminine, procollagen IV. type. Less often used are enzymes participating in collagen synthesis: prolyl-4-hydroxylase,lysyl-hydroxylase, galactosyl-hydroxylysyl-glucosyl-transferase, monoaminooxidase and N-acetyl-beta-D-glucoseaminidase. Breakdown of collagen is a multienzymatic process, catalysed by collagenases and other proteolytic enzymes. Decreased activity of collagenase is a supporting factor of cirrhosis development. Cirrhosis may be connected also with the levels of inhibitors such as e.g. serum/tissue? inhibitor of metalloproteinase. Biochemical markers of fibrogenesis are useful in regular monitoring of disease development and treatment effectivness and should be an inseparable part of progression assessment in all chronic hepatopathies. (Fig. 3, Ref. 49.)