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The genomes of two bacteria, Legionella polyplacis and Candidatus Riesia pediculischaeffi, lice endosymbionts, were examined and compared. Preserved genes were identified, assigned to appropriate metabolic pathways, and listed in an electronic attachment table. Completeness and functionality were assessed for individual metabolic pathways. Based on the results, metabolic maps were created for both bacteria

Waldenström macroglobulinemia is defined by the presence of monoclonal immunoglobulin IgM type (M-IgM) and evidence of lymphoplasmacytic bone marrow infiltration. The disease has an indolent course, the treatment is only initiated when the disease has begun to damage its carrier. The following symptoms are regarded as proven indications for initiating therapy: B symptoms, symptomatic lymphadenopathy, splenomegaly, anemia with hemoglobin below 100 g / l or thrombocytopenia100 × 10(9)/l, caused by lymphoplasmacytic bone marrow infiltration. Frequent indications for initiating treatment include clinical evidence of hyperviscosity or cryoglobulinemia. M-IgM tends to have a character of autoantibody reaching up to 50 %, which may harm the organism, and therefore any proven damage to the organism by an autoimmune activity of M-IgM is also an indication for treatment. The text includes an overview of rare and very rare types of damage to the organism by M-IgM autoimmune activity. A combination of rituximab, cyclophosphamide and dexamethasone (RCD) is recommended for the initial treatment, possibly extended to R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone). In our cohort of 43 patients the therapy involving a combination of R-CHOP achieved 3 (8.1 %) complete remissions and 31 (83.8 %) partial remissions. The remission in 75 % of the patients lasted more than 3 years. In case of recurrence after2 years, the same therapy can be used, in case of a relapse within a shorter period of time different treatment schedules are recommended. High-dose chemotherapy with an autologous transplant of stem cells obtained from peripheral blood is only recommended after the first recurrence for people under 65 years of age without contraindications. The text analyses the benefits of the new drugs for the treatment of Waldenström macroglobulinemia (bendamustine, thalidomide, lenalidomide, ibrutinib and high-dose chemotherapy).

Primary myelofibrosis (PMF) belongs to Ph- myeloproliferative diseases. The only curative treatment is hematopoietic stem cell transplantation (HSCT). Conservative treatment options comprise supportive care, especially administration of red blood cell and platelet transfusions, and medication. Hydroxyurea, interferon α, anagrelide, corticosteroids, androgens, or inhibitors of angiogenesis (thalidomide, lenalidomide, pomalidomide) may be used for treatment of PMF, depending on the clinical stage and disease symptoms present. Also splenectomy or radiotherapy of enlarged spleen have palliative potential. JAK2 kinase inhibitors represent a novel class of drugs with a very dynamic development. Ruxolitinib, an oral selective inhibitor of JAK1 and JAK2 kinases, has shown high efficacy in patients with high-risk PMF (or with myelofibrosis following polycythemia vera or essential thrombocythemia) to ameliorate disease symptoms and to reduce splenomegaly in randomized trials COMFORT-I and COMFORT-II. Long-term monitoring of the enrolled patients demonstated prolongation of overall survival. The drug is well-tolerated, the most common side effects of treatment with ruxolitinib being deepening of thrombocytopenia and temporary worsening of anemia. The current review deals with the place of JAK2 inhibitors (and the only drug already approved for clinical use - ruxolitinib) in the management of PMF, as an addendum to the Summary of recommendations for the diagnosis and therapy of BCR/ABL-negative myeloproliferations of the Czech Hematological Societys CZEMP.

The article summarizes the basic facts about the pharmacokinetic profile, metabolism and drug interactions of rilpivirine (RPV). This is the latest orally administered second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for antiretroviral-naive patients with HIV-1 infection. Conformational flexibility and adaptability are the factors that dominantly determine the high resistance barrier of RPV and are the unique features of diarylpyrimidine inhibitors (DAPY inhibitors - 2nd generation NNRTIs). Multicentre studies ECHO and THRIVE are also reviewed. Current guidelines for the treatment of HIV/AIDS are mentioned as well as the role of RPV in current therapeutic regimens.

Chronic myeloid leukaemia (CML) is an example of a tumour disease, in which the discovery of its molecular principle resulted in the development of the specific targeted molecular treatment with the first representative being imatinib. The introduction of other tyrosine kinase inhibitors, nilotinib and dasatinib, into the clinical practice meant not only a revolutionary change in the treatment approach to CML but literally an epochal improvement of the prognosis and quality of life. The disease with an originally fatal prognosis in patients diagnosed in the chronic stage has changed into a disease with the expected survival rate median estimated to be more than 25 years.

Chronic lymphocytic leukemia (CLL) is the most frequent, yet by conventional therapy still incurable, leukemia in the Western world. Accumulating evidence of the role of B cell receptor (BCR) pathway in CLL B cell bio-logy suggests the possible use of BCR inhibitors for targeted therapy. Recently published results of clinical trials of three different molecules (fosfamatinib, ibrutinib and GS 1101) targeting BCRassociated kinases (Syk, Btk, PI3K) showed impressive clinical activity in CLL. These findings will likely modify treatment approaches for chronic lymphocytic leukemia and some other B cell lymphomas in the near future. Herein, we review the data on BCR pathway deregulation in malignant CLL B cells, and the results of clinical trials utilizing fosfamatinib, ibrutinib and GS 1101.

Two clinical trials--CORONA and GISSI-HF--have been conducted to resolve uncertainties about the effects of statins in patients with chronic heart failure and justified suspicions that treatment with statins in these patients might be detrimental. The CORONA trial researched the effects of 10 mg rosuvastatin compared to placebo on the incidence of serious cardiovascular events in 5,011 patients with systolic heart failure of ischemic aetiology, above 60 years of age and in the NYHA functional class II-IV. Even though rosuvastatin reduced the mean LDL-cholesterol plasma concentrations by 45.0% (p0.001) and high-sensitivity C-reactive protein (hsCRP) concentrations by 37.1% (p0.001), the incidence of cardiovascular events was not importantly affected (HR = 0.92; p = 0.12). Rosuvastatin had no effect on overall mortality. The treatment resulted only in a reduction of the number of hospitalizations for cardiovascular causes (p0.001). The GISSI-HF trial involved 4,574 patients with chronic heart failure irrespective of aetiology and the ejection fraction value randomised to take either 10 mg of rosuvastatin or placebo. The results were almost identical. Rosuvastatin had no effect on the incidence of the primary end-point--the sum of cardiovascular mortality and hospitalizations (HR = 1.01; p = 0.903). The overall mortality was not affected either. Administration of rosuvastatin in both studies was safe, the number of adverse events, including myopathies and renal failure, was no different from placebo. However, recent results from the CORONA trial subtrials have suggested that important interactions exist in patients with chronic heart failure between the effects of rosuvastatin and natriuretic peptide and hsCRP plasma concentrations. Rosuvastatin provides clinical benefit in patients with relatively low concentrations of natriuretic peptides, i.e. relatively well-controlled, while it has no clinical effect in patients with high natriuretic peptide concentrations. Similarly, rosuvastatin provides clinical benefit in patients with high hsCRP but has no effect in patients with normal hsCRP (2 mg/l).

Chronic myeloid leukemia in blast phase (BP) is resistant to chemotherapy and majority of patients die within 6 months. Inhibitor Bcr-Abl tyrosine kinase imatinib mesylate dramatically improved outcome of patients in chronic phase (CP) and is also effective in BP of CML. The prognosis of patients treated with imatinib in BP is worse than in CP. High platelet counts are often observed at diagnosis or in the subsequent course of the CML in about 25% of patients. Thrombohemorrhagic complications associated with the thrombocythemia may be serious. Anagrelide selectively reduces circulating platelets and is used in treatment of thrombocythemia in chronic myeloproliferative disorders. Efficacy and safety of combination imatinib mesylate with anagrelide was demonstrated in chronic and accelerated phase of CML. No study about the use of imatinib with anagrelide in BP has been found. 51-year-old white man with CML presented in blast phase was followed for 4 years. Imatinib mesylate in dose of 600 mg p.o. qd. was administered after the failure of initial chemotherapy. The patient was treated with imatinib for 45 months, 14.5 months in combination with anagrelide. Partial hematologic response in duration of 33 months was induced by imatinib, cytogenetic response was not reached. Imatinib-resistant thrombocythemia was controlled with anagrelide in dose of 0.5-1 mg p.o. qd. No thrombohemorrhagic complications were observed. The patient tolerated the combination of imatinib and anagrelide well and long-term survival gave him the chance of treatment with the new tyrosin kinase inhibitor (dasatinib).

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by an abnormal fusion gene BCR-ABL. BCR-ABL encodes a constitutively active Bcr-Abl tyrosine kinase, which is required and sufficient for cellular transformation. Bcr-Abl is, therefore, an ideal target for pharmacotherapy. Imatinib Mesylate (Glivec) is a specific inhibitor of Bcr-Abl kinase. Imatinib shows high efficiency and low toxicity in treatment of CML patients. The main problem of imatinib treatment is the development of resistance. The mechanisms of resistance can be divided into two groups. The first group is characterized by reactivation of Bcr-Abl kinase in spite of continual imatinib presence. This can be caused by BCR-ABL amplification, overexpression or mutation in Abl kinase domain. Imatinib might not even reach the target Bcr-Abl protein (possible causes: drug efflux or imatinib binding to alpha1-acid glycoprotein). In the second group of resistance mechanisms, the Bcr-Abl kinase is inhibited but the resistance is maintained by other signal transducers (e.g. Src kinases). Standard cytogenetics as well as assay evaluating the phosphorylation status of Bcr-Abl substrate and/or sequencing of Abl kinase transcript can be used to test the mechanism of resistance. Treatment of patients can be re-evaluated on the basis of the status of IM resistance.

Among novel promising approaches to anticancer therapy belongs the targeting inhibition of signal transduction. This review outlines present-day experiences with imatinib (Glivec), a potent inhibitor of the tyrosine kinases bcr-abl, c-kit and platelet-derived growth factor receptor kinase. Due to inhibition of bcr-abl tyroxine kinase, imatinib has rapidly become the standard therapy for chronic myelocytic leukemia; inhibition of c-kit receptor explains its effectivity in the treatment of patients with gastrointestinal stromal tumors. Another known target of imatinib is tyrosine kinase of PDGFR, which is activated in numerous malignancies, particularly in dermatofibrosarcoma protuberans. Discovery of the novel fusion gene in hypereosinophilic syndrome (FIPILI-PFGFRA, whose product is an imatinib sensitive protein kinase) permitted to treat successfully this event. Possible combination of imatinib with conventional chemotherapeutic drugs and other key signal transduction inhibitors are mentioned.

The new knowledge in molecular biology and pathophysiology of chronic myeloid leukemia enabled the development of imatinib mesylate (Glivec, formerly STI571). Imatinib potently inhibits several protein tyrosine kinases, including BCR-ABL, c-Kit, and PDGF receptor. Imatinib blocks the phosphorylation of downstream target proteins and interrupts the malignant transformation leading to the development of CML. Phase I and II studies demonstrated that imatinib is highly effective and well tolerated in all phase of CML. We got our experience with imatinib on more than two-year monitoring 34 patients within the Expanded Access Study CST1571 0113. Imatinib 400 mg/d was administered orally to 10 women and 24 men in median age of 53 years (22-70) who were hematologically (n = 9) or cytogenetically (n = 13) resistant, cytogenetically refractory (n = 3) or intolerant (n = 9) to interferon alpha. The median follow-up time was 97.5 weeks (23-115), the median time from CML diagnosis to the start of the study was 32.3 months (6-140.5). Complete hematologic response was achieved in 33 of 34 (97%) pts, total major cytogenetic response (complete plus major) in 21 of 33 (63%) pts. Cytogenetic relapse was observed in 2 of 33 pts (6%), cytogenetic progression in 4 (12%) pts. Non-hematologic toxicity was mild (grade 1 or 2) and no patient was excluded from the study due to it. Hematological toxicity grade 3 limited dose of imatinib in 26% of patients and probably caused lower rate of cytogenetic responses in heavy pretreated patients. Both quantitative RT-PCR methods (competitive RT-PCR and real-time RT-PCR Light-Cycler) were found useful to monitor patients with CML on imatinib therapy. Our results confirmed high efficacy and safety of imatinib in late-chronic phase CML patients failing prior interferon therapy. The lower incidence of hematological toxicity and higher rate of cytogenetic responses in patients treated with imatinib in early-chronic phase CML justify according to our opinion the recommendation to administer imatinib early after the diagnosis of CML in patients who are not indicated for allogeneic transplantation.

Chronic myelogenous leukemia (CML) has been described in the middle of the 19th century. It took further 100 years to the time of the discovery of the first cytotoxic drugs. Ph1 chromosome, the cytogenetic hallmark of CML, has been described in 1960, however, the majority of important discoveries on the molecular level has been done in the 1980s' and later. The chromosomal translocation t(9;22)(q34;q11) is absolutely crucial for CML and leads to the chimeric gene and protein BCR-ABL. The ABL protein possesses the tyrosine kinase activity, which is deregulated in the BCR-ABL protein, leading to the cascade of further pathological processes in the leukemic cells and causing eventually their malignant transformation. In the 1990s, the drug STI 571 has been synthesized, which is a potent inhibitor of the ABL tyrosine kinase activity. The data so far published concerning clinical effects of STI 571 are remarkable and very encouraging. The drug seems to be very safe and has only limited toxicity. It must be emphasized, however, that STI 571 has been clinically tested only since 1998. Moreover, from the mechanisms of action it is clear, that STI 571 influences the secondary, not the primary cause of the CML. Nevertheless, it is without any doubts that the development of new anti-cancer drugs will be done on this non-cytotoxic principle.

We determined the yearly changes in coccidiosis extensity applying the results of an examination of 2707 rabbits performed in the years 1981-1984. A field trial was conducted to study the efficiency of the Czechoslovak anticoccidic drug Sulfakombin Spofa administered to control coccidiosis in small rabbit breedings. We made the calculations to find out the optimum time of administration of sulphonamide substances. We discuss certain factors that influence in a decisive way the changes in coccidiosis extensity in rabbit breedings.