ДУБ М.ЗАЛІЗНЯКА: З ІСТОРІЇ ПАМ’ЯТКООХОРОННОЇ РОБОТИ

Стаття присвячена проблемі вивчення, охорони та збереження пам’ятки природи тисячолітнього дуба М.Залізняка. В ній розглядаються етапи дослідження вікового дерева, основні пам’яткоохоронні заходи, проведені для підтримки його життєдіяльностіThis article is about a problem of investigation, saving and protection the monument of nature the millennial oak of M.Zaliznyak. It describes about the stages of research of the tree, the main protection measures in order to obtain it activit

Metabolic Profiling of S-praziquantel: Structure Elucidation Using the Crystalline Sponge Method in Combination with Mass Spectrometry and Nuclear Magnetic Resonance

Praziquantel (PZQ) is the drug of choice for treatment of the neglected tropical disease schistosomiasis. Although the drug has been extensively used over several decades and its metabolism well studied (several oxidative metabolites are known from literature), the knowledge of the complete structure of some of its metabolites remains elusive. Conventional techniques, such as nuclear magnetic resonance or liquid chromatography mass spectrometry were used in the past to investigate phase I and phase II metabolites of PZQ. These techniques are either limited to provide the complete molecular structure (liquid chromatography mass spectrometry) or require large amount of sample material (NMR), which are not always available when in vitro systems are used for investigation of the metabolites. In this study, we describe new structures of S-PZQ metabolites generated in vitro from human liver microsomes using the crystalline sponge method. After chromatographic separation and purification of the oxidative metabolites, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis was conducted to narrow down the position of oxidation to a certain part of the molecule. To determine the exact position of hydroxylation, singe-crystal X-ray diffraction analysis of the crystalline sponges and absorbed analyte was used to identify the structure of S-PZQ and its metabolites. The crystalline sponge method allowed for complete structure elucidation of the known metabolites S-trans-4'-hydroxy-PZQ (M1), S-cis-4'-hydroxy-PZQ (M2) and S-/R-11b-hydroxy-PZQ (M6) as well as the unknown metabolites S-9-hydroxy-PZQ (M3) and S-7-hydroxy-S-PZQ (M4). For comparison of structural elucidation techniques, one metabolite (M3) was additionally analyzed using NMR. SIGNIFICANCE STATEMENT: The information content of the metabolic pathway of praziquantel is still limited. The crystalline sponge method allowed the complete structural elucidation of three known and two unknown metabolites of S-praziquantel, using only trace amounts of analyte material, as demonstrated in this study

Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma

Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n = 3448) from 47 organs including skin neoplasms (n = 323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy

Applied system analysis and technology of designing the software

An analogy is made between the stages of applied system analysis and the stages of software Engineerin

Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future

Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle

Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL). We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy

Omental infarction in the postpartum period: a case report and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Omental infarction is a rare and often misdiagnosed clinical event with unspecific symptoms. It affects predominantly young and middle aged women.</p> <p>Case presentation</p> <p>This is a case report of a 26-year-old Caucasian woman with spontaneous omental infarction two weeks after normal vaginal delivery.</p> <p>Conclusion</p> <p>Omental infarction is a differential diagnosis in the postpartum acute abdomen. As some cases of omental infarction, which are caused by torsion, can be adequately diagnosed via computed tomography, a conservative treatment strategy for patients without complications should be considered in order to avoid any unnecessary surgical intervention.</p

Commodification and ‘the commons’: the politics of privatising public water in Greece and Portugal during the Eurozone Crisis

In response to the Eurozone crisis, austerity and restructuring has been imposed on the European Union’s (EU) peripheral member states in order to receive financial bailout loans. In addition to cuts in funding of essential public services, cuts in public sector employment and further liberalisation of labour markets, this has also included pressure towards the privatisation of state assets. And yet, workers have not simply accepted these restructuring pressures. They have organised and fought back against austerity and enforced privatisation. Based on a historical materialist perspective and following a strategy of incorporated comparison, in this paper we will comparatively assess the struggles against enforced water privatisation in Greece and Portugal set against the background of the structuring conditions surrounding the Eurozone crisis

Uneven and combined development and unequal exchange: the second wind of neoliberal ‘free trade’?

With capitalist social relations emerging in a prior system of absolutist states in Europe, the outward expansion of capitalism through conditions of uneven and combined development became dependent on the existence of multiple political entities. States in turn are brought into relations of unequal exchange within the global economy. This article analyses the way in which current neoliberal ‘free trade’ policies are related to these fundamental capitalist dynamics, deepening further processes of uneven and combined development as well as unequal exchange