[What is the current treatment of patients with essential thrombocytopenia and other myeloproliferations accompanied with thrombocythemia [corrected] and what can be the predictive sign of the risk of thrombosis in such patients--a report from the registry of patients treated by Thromboreductine]. / Jak lécíme nemocné s esenciální trombocytemií a dalsími myeloproliferacemi provázenými trombocytemií a co muze být prediktivní známkou rizika trombózy u techto nemocných--zpráva z registru pacientu lécených Thromboreductinem.

The registry of patients treated with Thromboreductine (anagrelid) in the contributing centres in the Czech Republic has been updated with data on the patients receiving this medication since 2004. The original purpose of the registry was to record responses to Thromboreductine therapy and adverse drug reactions in patients with essential thrombocytopenia. However, data on additional Ph negative myeloproliferations, as well as data on cytoreductive therapies other than exclusively that using Thromboreductine has also been recorded in the course of its compilation, including data on combined regimes. At present, the database contains data on 421 patients, and valid conclusions can be drawn if the level of data filling is enhanced. Evaluation has been currently focused on the analysis of the risk of development of clinical symptoms of thrombosis and on the standards of treatment from the viewpoint of the achieved treatment response. Analyses of data from the registry corroborate the special importance of the proof of JAK2 mutation, and of the test for factor V Leiden mutation, and of protein of S for the assessment of the risk of thromboembolic complications. The output of the analysis confirms that anagrelid is a very efficient thromboreductive agent the administration of which is associated with a low incidence of non-serious adverse effects (10.9%). However, in spite of a fast response to therapy, the therapeutic goal consisting in the reduction of the platelet count below 400 (or below 600) x 10(9)/l, i.e. the complete (or partial) treatment response, is relatively slow to achieve. This is likely to be due to lack of radical corrections in the dosage of the drug for different reasons.

[Essential thrombocytemia and other myeloproliferations with thrombocytemia in the data of the register of patients treated with Thromboreductin till the end of 2006]. / Esenciálni trombocytemie a dalsí myeloproliferace s trombocytemií v údajích registru pacientu lécených Thromboreductinem do konce roku 2006.

Since 2005, registers of patients treated with Thromboreductin (anagrelid) kept by some centres in the Czech Republic have been supplied with data concerning patients whose treatment with this preparation started in 2004. The purpose of the register is to record responses to therapy by Thromboreductin and adverse events in patients with essential thrombocytemia and other myeloproliferations, and to subsequently analyse the data. Another objective is to detect predisposition to clinical symptomatology and disease complications. Apart from thrombocyte count, additional risk factors are monitored. The database currently contains data for 336 patients. Initial analyses of data from the register point to the fact that anagrelid is a highly effective thromboreductive agent the administration of which is associated with relatively low incidence of adverse events (11.8 %) of mild and usually transitory nature. The therapeutic objective is attained at a relatively slow rate (according to overall stratification under 400 or under 600 x 10(9)/l thrombocytes), which is probably due to insufficient dose adjustment.

Prognostic relevance of the FAB morphological criteria in chronic lymphocytic leukemia: correlations with IgVH gene mutational status and other prognostic markers.

Morphological examination is the routine first step in the diagnosis of hematological malignancies, including chronic lymphocytic leukemia (CLL). Atypical cell morphology according to the FAB criteria is known to herald disease progression. Several years ago, it was proposed that FAB morphology at diagnosis had a considerable prognostic impact. However, this proposal has not been widely adopted in practice. Thus we questioned the prognostic value of the morphological examination, which was performed retrospectively in 88 patients out of our 110 institutional registry patients (70 males and 40 females, median age 57 yrs) with CLL at diagnosis. We related the results to the more modern prognostic markers. Atypical FAB morphology was shown to correlate with IgVH gene mutation status, trisomy of chromosome 12 and deletion of 17p detected either by conventional G-banding or by fluorescence in situ hybridization (FISH) analysis. The correlation of FAB morphology with CD38 antigen expression or with the histopathological pattern of bone marrow infiltration was not significant. Overall survival (OS) data were available for 84 morphologically examined patients. The patients with atypical morphology (64 patients) had a significantly shorter OS (103 months) than the 20 patients presenting with typical CLL morphology (237 months; p=0.03). Only the mutation status of IgVH genes correlated more closely with OS (p=0.002). Of note, there was no leukemia-related death within "unmutated" cases who had typical FAB morphology (p=0.14), and vice versa, the mutation status had a significant prognostic impact within the morphologically atypical cases (p=0.01). Thus FAB morphology and the mutation status may yield complementary prognostic information. OS was affected both by the presence of cytogenetic aberrations (p=0.03) - most adversely by deletions of 17p and 11q, and by CD38 expression (p=0.003). We conclude that careful examination of peripheral blood smears according to FAB is a simple, cheap and valuable tool in the first-line assessment of prognosis of CLL patients and should not be overlooked even in 3rd millennium when more sophisticated prognostic markers are at hand. This ought to be confirmed in larger prospective studies with multivariate analysis of data.

[The use of quantitative assessment of Wilms tumour gene 1 for monitoring of residual disease in acute myeloid leukemia patients]. / Uzití kvantitativního stanovení exprese genu wilmsova tumoru 1 pro monitorování reziduální nemoci pacientu s akutní myeloidní leukémií.

BACKGROUND: Despite a considerable effort, the majority of acute myeloid leukaemia (AML) patients do not have a suitable specific molecular marker for monitoring minimal residual disease (MRD). The results of some studies suggest the Wilms tumour gene (WT1) as a possible molecular marker of MRD. METHODS AND RESULTS: We measured the expression of WT1 at diagnosis and during treatment of the acute myeloid leukaemia (AML) patients. The expression of WT1 was measured by the quantitative real-time RT-PCR in peripheral leukocytes from 56 AML at diagnosis and 7 patients with AML transformed from myelodysplastic syndromes (MDS). The WT1 expression was significantly elevated (up to 3 orders of magnitude) in peripheral blood samples (PB) of AML patients at diagnosis compared to PB samples of healthy donors (P < 0.0001). The level of WT1 expression depends particularly on FAB AML subtype, with the highest being found in AML patients with subtypes M4, M1, M3 and AML transformed from MDS. Conversely, AML patients with M2 and with the presence of AML1/ET0 at presentation showed a significantly lower expression of the WT1 gene compared to the remaining AML patients at presentation (P = 0,005). Further, sequence samples of 12 AML patients under long-term surveillance were tested for the WT1 expression in parallel with the expression of specific MRD markers--fusion genes: AMLI/ETO, PML/RARalpha and CBFB/MYH11. The levels of WT1 gene expression and the above specific fusion genes significantly correlated. Moreover, 14 patients without the specific MRD marker were tested for the WT1 expression. The results show that haematological relapses were associated with the rise of expression of the specific fusion genes and with the WT1 gene expression. The rise of WT1 expression above the level seen in leucocytes from peripheral blood and/or bone marrow of healthy donors--in four patients under long-term surveillance the "molecular relapse" predicted ongoing haematological relapses as early as 2 months in advance. CONCLUSIONS: Our results, in accordance with some of the previously published ones, show that WT1 expression seems to be a suitable marker of minimal residual disease in AML patients.

[Anagrelide in the treatment of essential thrombocythemia (ET) and other myeloproliferative disorders with thrombocythemia based on data from patient register in the CR]. / Anagrelid v lécbe esenciální trombocytemie a dalsích myeloproliferací s trombocytemií sledovaných v registru pacientu v CR.

Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.

[Production of active oxygen by neutrophils in patients with cancer of the esophagus and stomach before and after surgical interventions].

The state of the oxygen-depended antimicrobial activity of neutrophils on oncologic patients was studied. Production of active oxygen by non-activated and activated neutrophils of peripheral blood from 19 patients (the average age of 56 years, 16 males and 3 females) with esophageal cancer and cancer of the stomach and metastasis to the esophagus was recorded by chemiluminescence before and after surgical interventions (transpleural gastrectomy, Lewis type operation) on the 1st, 3rd and 7th days after the operations. The oxygen-depended antimicrobial activity of the neutrophils was investigated by their ability to produce active oxygen when incubated with opsonized zymosan and N-formyl-methionyl-leucyl-phenylalanine. Luminol chemiluminescence recorded the whole pool of active oxygen and showed the summary activity of myeloperoxidase and NADPH-oxidase, while luceginin chemiluminescence measured formation of superoxide anion radical (*O(-)2) and evaluated the activity of NADPH-oxidase. The results showed that the procedure provided estimation of the functional state of the neutrophil leukocytes and their ability to produce active oxygen. Impairment of the myeloperoxidase- and NADPH-depended production of active oxygen by non-activated and activated neutrophils observed before operations resulted in altered synthesis of active oxygen after the surgery. This is one of the leading factors of the infection development in the end. Detection of the myeloperoxidase- and NADPH-depended production of active oxygen could be of help in revealing the groups of risk among patients at the stage of the preoperative examination and serve as a prognostic factor of the development of severe infectious complications during the postoperative period.

[Role of tissue glycolysis in combined exposure to hypercapnia, hypoxia and hypothermia]. / Znachenie glikoliza v tkaniakh pri sochetannom vozdeistvii giperkapnii, gipoksii i gipotermii.

The amount of metabolites of the glycolytic way of carbohydrates transformation and the enzymatic activity were studied in the tissues of brain, myocardium, liver, skeletal muscles, and the blood serum of rats subjected to cooling in conditions of gradually increasing concentrations of CO2 and decreasing concentrations of O2. Single as well as repeated actions of these factors entailed changes of the substrates under study and of some enzymatic activity which revealed a moderate intensification of the glycolysis within the general rearrangement of metabolism during adaptation to sharp hypoxia under the above conditions.

[The beta-glucuronidase activity in the blood cells and serum of patients with systemic lupus erythematosus]. / Aktivnost' beta-gliukuronidazy v kletkakh i syvorotke krovi bol'nykh sistemnoi krasnoi volchankoi.

Beta-glucuronidase (beta-GU) activity and protein concentration were measured in peripheral blood cells (neutrophils and mononuclear cells) and blood serum of patients with systemic lupus erythematosus (SLE). SLE patients were found to tend towards decrease of beta-GU activity in neutrophils and to an appreciable increase thereof (2-fold) in blood serum. The concentration of protein in both neutrophils and mononuclear cells was within normal. Substantial changes in beta-GU activity were seen in SLE patients with trophic disorders (a significant decrease of the enzyme in neutrophils and a rise in blood serum). These patients also manifested a noticeable reduction of protein concentration in mononuclear cells. The measurement of beta-GU activity in blood cells can be used for the choice of adequate therapy in the course of the treatment of SLE patients.

[Zonal distribution of haptoglobin and ceruloplasmin synthesis in the liver]. / Zonal'noe raspredelenie sinteza gaptoglobina i tseruloplazmina v pecheni

Effect of hepatotoxic agents (carbon tetrachloride and dimethyl nitrosamine) on the rate of the haptoglobin and ceruloplasmin synthesis in liver tissue was studied. In impairment of hepatocytes in the central zone of liver lobes, the distinct decrease in content of haptoglobin was shown to occur with a simultaneous increase in content of ceruloplasmin in blood serum. When parenchyma of the central zone of liver lobes regenerated, the haptoglobin content tended to normalization. The data obtained suggest that the synthesis of haptoglobin and ceruloplasmin is carried out in different zones of liver tissue lobes: haptoglobin is mainly found in the central zone and ceruloplasmin -- in the peripheral one.

[Role of histiocytic and parenchymatous elements of the liver in biosynthesis of reactive blood glycoproteins (haptoglobin and ceruloplasmin)]. / Rol' gistiotsitarnykh i parenkhimatoznykh élementov pecheni v biocinteze reaktivnykh glikoproteinov krovi (gaptoglobina i tseruloplazmina).

Synthesis of haptoglobin and ceruloplasmin was found to occur in liver parenchyma under conditions of obligatory participation of the tissue mesenchymal structural elements. Dependence of the blood glycoproteins hyperproduction on the processes of proliferation, occurring in hystiocytic structural elements of liver, was detected after administration into rabbits of zymosan, which stimulated the reticuloendothelial cells, of turpentine (causing inflammation in subcutaneous fatty tissue) or of intracellular cytoplasmic soluble antigens of beta-haemolytic streptococcus A.

[Proteolytic activity of blood cells in rheumatoid arthritis]. / Issledovanie proteoliticheskoi aktivnosti kletok krovi pri revmatoidnom artrite.

Collagenolytic and neutral caseinolytic activities were studied in lysates of neutrophils, mononuclear cells and thrombocytes of patients with rheumatoid arthritis considering the steps and duration of the disease, before and after medical treatment. 5 healthy persons and 18 patients with rheumatoid arthritis were investigated. Specific caseinolytic activity (per 1 mg of protein) was increased in the patients neutrophils and monocytes 2.2- and 3.2-fold, respectively, while the activity per 10(6) cells was increased 1.5- and 2.2-fold, respectively. Specific collagenolytic activity was increased 1.4-fold in neutrophils and monocytes, whereas the activity per 10(6) neutrophils was increased by 20% and per 10(6) monocytes--near normal values. In thrombocytes collagenolytic activity was decreased by 40% and caseinolytic activity was similar to controls. Concentration of protein was decreased 1.5-fold in neutrophils and monocytes of the patients as compared with healthy persons. Proteinases are of importance in pathogenesis of rheumatoid arthritis and collagenolytic activity correlated most distinctly with development of the disease. After medical treatment collagenolytic activity was normalized in the patients cells studied, while caseinolytic activity was markedly decreased but remained above control values. Experiments with proteinase inhibitors enabled to detect major types of neutral proteinases in blood cells of patients with rheumatoid arthritis and to find some differences in the enzyme patterns in various blood cell populations.

[Haptoglobin and ceruloplasmin in systemic scleroderma]. / Gaptoglobin i tseruloplazmin pri sistemnoi sklerodermii.

Content of haptoglobin and ceruloplasmin was estimated in blood serum of 23 patients with sclerodermia systematica. A statistically distinct decrease in ceruloplasmin concentration was observed in blood of the patients, whereas content of haptoglobin was markedly increased; this phenomenon reflects a level of the pathological process activity. The proteins are synthesized in various zones of liver lobes: haptoglobin--in the central zone, ceruloplasmin - in the peripheral one. Decrease in content of ceruloplasmin in blood of patients with sclerodermia systematica was due to impairment of hepatocytes, localized in peripheral parts of liver lobes.

[The total proteolytic and collagenolytic activity in the blood cells of patients with systemic scleroderma]. / Izuchenie obshchei proteoliticheskoi i kollagenoliticheskoi aktivnosti v kletkakh krovi bol'nykh sistemnoi sklerodermiei.

Collagenolytic (CA) and neutral caseinolytic activity (NCA) was studied in extracts from blood cells (neutrophils, mononuclear cells and platelets) of patients suffering from systemic scleroderma (SSD). 23 persons were examined. Of these, 15 had local skin lesions, 8 diffuse lesions. CA, both specific and per 10(6) cells was found to be dramatically decreased (2-4-fold) in all blood cells, whereas NCA was increased in neutrophils and mononuclear cells; in platelets, it remained within normal. The amount of protein in neutrophils and mononuclear cells was lowered 1.2 and 2-fold respectively. In diffuse skin lesions, the amount of protein in cells was lower than in local lesions. It should be noted that in SSD patients examined, the inflammatory process was unmarked. Therefore, the data on substantial changes in proteolytic activity cannot be related to the inflammatory process. A reverse correlation was established between CA in neutrophils and circulating immune complexes as was a reverse correlation between CA in mononuclear cells and blood antinuclear factor. The data presented indicate that proteinases are an important factor of the pathogenesis in SSD. Apparently, SSD is characterized not only by enhanced synthesis of collagen but also by a dramatic reduction of the activity of enzymes that specifically hydrolyze this group of proteins, which leads to a decrease of collagen catabolism and hence, to the development of fibrosis in tissues.

[Clinical value of determining beta-glucuronidase and glycosaminoglycans in blood cells and biological fluids in patients with rheumatoid arthritis]. / Klinicheskoe znachenie opredeleniia beta-gliukuronidazy i glikozaminoglikanov v kletkakh krovi i biologicheskikh zhidkostiakh u bol'nykh revmatoidnym artritom.

Patients with proved rheumatoid arthritis (RA) demonstrated changes in the activity of beta-glucuronidase and the concentration of glycosaminoglycans (GAG) in the blood formed elements and biological fluids showing correlation with peculiarities of the RA course. The content of beta-glucuronidase and GAG in biological fluids well reflected the activity of an inflammatory process. Significant differences in the level of beta-glucuronidase and GAG in blood cells of patients with the articular type of RA and systemic manifestations of disease were revealed.

[Glycosaminoglycans and beta-glucuronidase in peripheral blood cells and biological fluids of patients with rheumatoid arthritis]. / Glikozaminoglikany i beta-gliukuronidaza kletok perifericheskoi krovi i biologicheskikh zhidkostei pri revmatoidnom artrite.

Content of glycosaminoglycans and beta-glucuronidase activity were measured in leukocytes, blood serum and urine of patients with rheumatoid arthritis. Concentration of glycosaminoglycans was increased in blood serum and urine of the patients. The most distinct increase as compared with healthy persons in content of these substances was found in leukocytes of the patients with joint form of rheumatoid arthritis. Activity of beta-glucuronidase was also elevated in cells of peripheral blood, whereas content of protein was decreased in these cells. The enzymatic activity was reduced in the fraction of polymorphonuclear leukocytes of the patients as shown by estimation of the activity per 10(6) cells after fractionation using the Ficoll-verografin procedure. Deficiency of beta-glucuronidase activity in polymorphonuclear leukocytes appears to be among the factors responsible for excess of glycosaminoglycans in blood serum and urine of the patients as well as for chronic inflammation under conditions of rheumatoid arthritis.

[Importance of beta-glucuronidase activity and glycosaminoglycan concentration in synovial fluid in patients with rheumatoid arthritis in estimating local inflammation]. / Znachenie aktivnosti beta-gliucuronidazy i kontsentratsii glikozaminoglikanov v sinovial'noi zhidkosti u bol'nykh revmatoidnym artritom v otsenke mestnoi vospalitel'noi aktivnosti.

In 30 patients with rheumatoid arthritis, the activity of beta-glucuronidase and the content of sulfated and non-sulfated glycosaminoglycans (GAG) were measured in synovial fluid (SF) and in the cells of SF. It has been established that as the local inflammation increases, the activity of the enzyme and the content of sulfated GAG in SF also rise. This is accompanied by simultaneous reduction of beta-glucuronidase activity in the cells and by the drop of the hyaluronic acid content in SF.

[The mechanism of the action of laser therapy in rheumatoid arthritis]. / K mekhanizmu deistviia lazernoi terapii pri revmatoidnom artrite.

48 patients with rheumatoid arthritis (RA) were exposed to He-Ne laser radiation. Due to the course of the above laser therapy the patients displayed reduced levels of E and F2 alpha prostaglandins, a trend to a decrease of lipid peroxidation products, glycosaminoglycans and collagen-peptidase activity. This evidences for suppression of the inflammation and destruction in the connective tissue. Catalase activity in red cells enhanced. The authors point to high efficacy of low-intensity He-Ne laser in moderate rheumatoid inflammation.

[Establishment of the most efficient fatty acid composition of dietary fats in an animal experiment]. / Obosnovanie ratsional'nogo zhirno-kislotnogo sostavo pischchevykh zhirov v éksperimente na zhivotnykh.

The paper is concerned with studying the optimal fatty acid composition of food fat. The experiments were carried out on growing male rats with an initial medium body weight of 72-83 g. The acid content in experimental fat mixtures prepared on the basis of sunflower, olive, coconut oils and beef fat was made different within the preset ranges. These mixtures served as the diet fat component, which was given to rats in an amount of 30% in terms of caloricity. The follow-up study was performed for 12-14 weeks. Examination of a complex of the biological parameters made it possible to establish that the food fat if balanced in the acid content and possessing the highest biological properties is to include 20% linolic acid, 50% oleic acid and 30% saturated fatty acids. The ratio of medium- and high molecular weight fatty acids is to be equal to 1:1.

[Biological properties of vegetable oils containing linolenic acid (18:3 omega 3)]. / O biologicheskikh svoistvakh rastitel'nykh masel, soderzhashchikh linolenovuiu kislotu (18:3 omega 3).

Experiments on growing albino male rats were made to study the food value of the vegetable oils: soybean and rapeseed ones containing different quantities of linolenic acid. These oils were included in the animals' diet in the amount of 25% with respect to caloric value for 12-13 weeks. It has been established that as the content 18:3 omega 3 in the food fat was reduced, the metabolism of fatty acids in the body improved, manifesting in a noticeable rise of the efficacy of food fatty acids metabolization. This process was affected not only by the ratio 18:3 omega 3 and 18:2 omega 6 in the food fat but also by the total balance in it of fatty acids.

[Chemical and biological properties of grape seed oil]. / Khimicheskii sostav i biologicheskie svoistva masla iz semian vinograda.

Biological properties of grape seed oil, included into the ration of animals in the amount of 25% of calorie value during 11 weeks, were studied in growing male rats. It has been established that deodorized grape seed oil is close to sunflower oil by its chemical and biological properties. The possibility of using grape seed oil as full value food vegetable oil has been validated.