Ruxolitinib in contemporary treatment of myelofibrosis

Introduction: Myelofibrosis (MF) is a rare chronic Ph(-) myeloproliferative neoplasm that can man­ifest as a primary disease or secondary to polycythaemia vera or essential thrombocythaemia. MF results from dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcrip­tion (STAT) pathway and the most common mutations are JAK2V617F and in the Myeloprolifera­tive leukaemia protein (MLP) gene. For decades, the therapy has been mainly palliative (Immuno­modulators, DNA methyltransferase inhibitors, colony stimulating factors) with none of them lead­ing to complete remission. Ruxolitinib is a new generation JAK1 and JAK2 inhibitor having a remark­able impact on bone marrow fibrosis (BMF) and splenomegaly in patients with high and intermedi­ate-risk MF. The aim of this research is a discussion of the mechanisms of actions of Ruxolitinib and its efficacyMaterials and methods: A documentary approach is used. A targeted analysis of publications, avail­able in PubMed and ScienceDirect is presented. The keywords used to collect the data were: `ruxoli­tinib myelofibrosis` (5 publications); `ruxolitinib mechanisms of actions` (3 publications); `ruxoli­tinib trials` (4 publications).Results: Ruxolitinib has dose-dependent efficiency on BMF, spleen size and constitutional symp­toms like anaemia, fever and weight loss. Ruxolitinib`s effects are mediated by the following molec­ular mechanisms: a decrease in activation, proliferation and migration of Natural killer and den­dritic cells, a reduction of proinflammatory cytokines like Interleukin-1, Tumor Necrosis Factor-α, Interferon-γ; an increase in plasticity and titre of Th17 cells; stabilization of the serum albumin and total cholesterol that results in weight gain. `Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment` I and `Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment` II are phase III trials which demonstrate how Ruxolitinib makes a reduction of 35% in spleen size and 33% in le­thal exit.Conclusion: Ruxolitinib is a good example of how targeted therapy ameliorates progression free sur­vival and overall survival

Anticancer potential of artemisia annua

Introduction: Cancer is one of the major challenges of medicine. Chemotherapy, surgery, radiother­apy are available treatment methods, but in many cases have limited efficacy. In recent years, the po­tential anticancerogenic effects of some plants have been investigated. One of these plants is Artemis­ia annua (AA) - sweet Wormwood. Its main chemical component is artemisinin.Materials and methods: The aim of this article is a discussion of molecular mechanisms of antican­cer effects of artemisinin. A documentary approach is used. A literature analysis of articles, available in Pubmed and ClinicalKey is presented. The keywords used for collecting of data were: `artemis­inin cancer` (5 articles); `artemisinin mechanism of action`(3 articles) and `artemisinin breast can­cer` (4 articles).Results: Pharmacochemical investigations claim that the potential anticancer mechanisms of arte­misinin are: endoperoxide moiety (the peroxide bridge of artemisinin can react with the ferrous atom and produce free oxygen radicals that leads to Deoxyribonucleic acid (DNA) damage in tumor cells); cell cycle arrest (inhibition of cyclins and cyclin-dependent kinases (CDKs)), resulting in arrest of cancer cell in Growth2 phase/Metaphase); stimulating apoptosis and autophagy (promoting the re­lease of cytochrome 3 and the overexpression of proapoptotic gene B-cell-lymphoma-associated-X-protein(BAX)) , but also by activating caspase-3 and caspase-9) and anti-metastatic activity (reduc­ing angiogenesis growth factors like vascular endothelial growth factor). In vivo studies by rats with breast cancer (BC) show that following an application of artemisinin there is impressive decrease in tumor cell volume. In vitro studies with adenocarcinoma cell line implanted rat mammary glands present that artemisinin significantly retards the growth of tumor cells.Conclusion: In the future, after further investigation of its mechanisms of actions, safety and effi­ciency artemisinin and its derivatives could be a new class of anticancer agents as up-to-date there are randomized trials for colon cancer (Artesunate), acute myeloid leukemia (Artesunate+Dihydroar temisinin+Cytarabine) and BC

Pregnancy with Tetralogy of Fallot

Introduction: Tetralogy of Fallot is a congenital heart defect that is present at birth. It features four problems: a ventricular septal defect, pulmonary stenosis, a right ventricular hypertrophy  and an overriding aorta. The cause of the tetralogy of Fallot is not known and it is most often diagnosed in the first few weeks of life due to either a loud heart murmur or cyanosis. Children having a tetralogy spell will initially become extremely irritable in response to the critically low oxygen levels and may become sleepy or unresponsive if the severe cyanosis persists.The aim of our research was to evaluate the pregnancy outcome in women with tetralogy of Fallot. The study was a retrospective analysis of maternal and perinatal outcome in 3 women with TOF treated in a cardio-obstetric unit. One of the women with this uncorrected congenital heart defect had one child. Obstetric and cardiac complications were more frequent in the uncorrected tetralogy.Materials and Methods: A retrospective analysis of maternal and perinatal outcome of pregnancies in women with TOF who were seen in the obstetrics unit in Varna`s hospital - Maichin Dom. All women were supervised in the cardio-obstetric clinic under joint supervision of obstetrician and cardiologists. These women were kept under observation post partum.Results: The outcome of our research was that in the women with a corrected condition - there were 100% live births to term. In the uncorrected woman there was one preterm birth. There was 1 neonatal death in the uncorrected woman, too. No baby was determined to have a congenital anomaly, including congenital cardiac malformations.Conclusion: Tetralogy of Fallot carries substantial risk to mother and fetus. Surgical correction is associated with improved maternal and perinatal outcome. These patients need detailed pre-pregnancy evaluation and should be under joint supervision of an obstetrician, a cardiologist, a congenital cardiac surgeon, and an anesthetist