Przewlekła białaczka szpikowa jako drugi nowotwór mieloproliferacyjny u pacjentki z wieloletnim przebiegiem pierwotnej mielofibrozy

Chronic myeloproliferative neoplasms (MPN) can be categorised into Philadelphia-negative(Ph–) disorders and Philadelphia-positive (Ph+) chronic myeloid leukaemia (CML). Each ofthese neoplasms presents specific clinical and laboratory symptoms however occasionally thesediseases may coexist together, thus making classification difficult when such syndromes overlap.A case study is presented of just such an occurrence. This was a 44-year-old woman withprimary myelofibrosis (PMF) that had been recognised in 2004 according to obligatory WHOcriteria. After four years of follow-up the Ph chromosome appeared. Despite still having bonemarrow morphology characteristic of PMF, CML was found as shown by an atypical bonemarrow histology. A ten-month treatment with imatinib proved ineffective with complicationsarising of profound anaemia thereby requiring dose reduction, withdrawing the drug and redblood cell transfusion. It was only by administering nilotinib that the Ph+ clone was eradicated,however at the same time some abnormal Ph- clones were observed showing numerousmutations indicative of genetic instability. The clinical course and molecular biology resultsthen enabled recognition of two MPNs, namely PMF and CML, which had probably evolvedfrom two independent cell clones. This case therefore demonstrates that diagnosing MPN canbe challenging. The coexistence of two neoplasms should be taken into consideration in casespresenting an unusual clinical course and overlapping molecular abnormalities. Cytogeneticand molecular monitoring is thus important in such clinical cases. It allows not only a diagnosisMPN, but also new cell clones can be identified that lead to another MPN emerging as shownin this case report.Przewlekłe nowotwory mieloproliferacyjne (MPN) dzieli się na choroby bez obecności chromosomuFiladelfia (Ph) i przewlekłą białaczkę szpikową (CML) z obecnością chromosomu Ph.Chociaż każdy z tych nowotworów cechuje się określonymi objawami klinicznymi i laboratoryjnymi,to niekiedy choroby te mogą współistnieć, prezentując klinicznie i trudne do klasyfikacjizespoły nakładania. Przedstawiono przypadek 44-letniej pacjentki, u której w 2004 rokurozpoznano, zgodnie z obowiązującymi kryteriami Światowej Organizacji Zdrowia, pierwotnąmielofibrozę (PMF). Po 4 latach obserwacji u chorej pojawił się chromosom Ph, ale obrazmorfologiczny szpiku pozostawał taki, jak w PMF. Rozpoznano wówczas CML o nietypowejprezentacji histologicznej szpiku. Leczenie imatynibem, trwające 10 miesięcy, było nieskutecznei powikłane głęboką niedokrwistością, wymagającą zmniejszania dawki, odstawiania lekui przetaczania koncentratów krwinek czerwonych. Dopiero włączenie nilotynibu spowodowałoeradykację klonu Ph(+), ale jednocześnie ujawniło kilka nieprawidłowych klonów Ph(–)z licznymi mutacjami, świadczącymi o dużej niestabilności genetycznej. Przebieg klinicznyi wyniki badań molekularnych pozwoliły na rozpoznanie dwóch nowotworów PMF i CML,które najprawdopodobniej rozwinęły się z dwóch niezależnych klonów komórkowych. Prezentowanyprzypadek dowodzi, że diagnostyka MPN nie zawsze jest łatwa, a w sytuacjach o nietypowymprzebiegu klinicznym i nakładających się aberracjach molekularnych należy brać poduwagę współistnienie dwóch nowotworów. Duże znaczenie w takich przypadkach ma monitorowaniecytogenetyczne i molekularne, które nie tylko umożliwia dokonanie właściwego rozpoznaniaMPN, ale również, co przedstawiono w niniejszej pracy, pozwala na identyfikacjęnowych klonów komórkowych prowadzących do rozwoju kolejnego nowotworu

Supplementation of Nutraceuticals from Dwarf Kiwi and Apple Improves Lipid Profile in Overweight Adults

(1) Background: Overweight and obesity are emerging global problems causing multiple health complications. Excessive fat tissue content leads to chronic inflammation, which is why antioxidative compounds that could potentially reduce these processes are possible agents that could be supplemented in order to prevent metabolic complications of overweight and obesity. Apples and dwarf kiwis are good sources of antioxidative agents such as quercetin and chlorogenic acid. The aim of this study was to assess if apple and dwarf kiwi nutraceutical supplementation can improve the metabolic parameters of overweight adults. (2) Methods: 43 participants were enrolled in the double-blinded pilot study: 21 in the supplementation group and 22 in the placebo group. The one 1000 mg nutraceutical capsule contained 10% Chopin apple peel extract, 10% whole dwarf kiwi fruit extract, 75% Chopin apple core extract, and 5% rapeseed peptides. The supplementation group received two capsules/day for 60 days. (3) Results: The supplementation of the apple and kiwi product resulted in a lowering of ALT in the supplementation group (from 29.65 ± 19.02 UI/L to 23.80 ± 13.76 UI/L; p = 0.01). Subgroup analysis in men and women showed a significant decrease in total cholesterol level (from 220.15 ± 36.69 mg/dL to 208.43 ± 37.09 mg/dL; p = 0.04), non-HDL cholesterol (from 161.17 ± 41.00 mg/dL to 145.69 ± 41.75 mg/dL; p = 0.02) and ALT (from 25.41 ± 12.05 UI/L to 19.07 ± 6.13 UI/L; p = 0.01) in women and triglycerides levels (from 212.74 ± 127.15 mg/dL to 155.63 ± 80.61 mg/dL; p = 0.047) in men. (4) Conclusions: The supplementation of nutraceuticals from apples and dwarf kiwi led to improvements in lipid profile. It can be a possible new agent for counteracting overweight metabolic complications, however, larger group studies and more detailed tests are needed to support these preliminary findings

Biological Control of Fusarium culmorum, Fusarium graminearum and Fusarium poae by Antagonistic Yeasts

The genus Fusarium is considered to be one of the most pathogenic, phytotoxic and toxin-producing group of microorganisms in the world. Plants infected by these fungi are characterized by a reduced consumer and commercial value, mainly due to the contamination of crops with mycotoxins. Therefore, effective methods of reducing fungi of the genus Fusarium must be implemented already in the field before harvesting, especially with alternative methods to pesticides such as biocontrol. In this study we identified yeasts that inhibit the growth of the pathogenic fungi Fusarium culmorum, F. graminearum and F. poae. Tested yeasts came from different culture collections, or were obtained from organic and conventional cereals. The greater number of yeast isolates from organic cereals showed antagonistic activity against fungi of the genus Fusarium compared to isolates from the conventional cultivation system. Cryptococcus carnescens (E22) isolated from organic wheat was the only isolate that limited the mycelial growth of all three tested fungi and was the best antagonist against F. poae. Selected yeasts showed various mechanisms of action against fungi, including competition for nutrients and space, production of volatile metabolites, reduction of spore germination, production of siderophores or production of extracellular lytic enzymes: chitinase and β-1,3-glucanase. Of all the investigated mechanisms of yeast antagonism against Fusarium, competition for nutrients and the ability to inhibit spore germination prevailed

Reduction of the Fusarium Mycotoxins: Deoxynivalenol, Nivalenol and Zearalenone by Selected Non-Conventional Yeast Strains in Wheat Grains and Bread

Mycotoxins, toxic secondary metabolites produced by fungi, are important contaminants in food and agricultural industries around the world. These toxins have a multidirectional toxic effect on living organisms, causing damage to the kidneys and liver, and disrupting the functions of the digestive tract and the immune system. In recent years, much attention has been paid to the biological control of pathogens and the mycotoxins they produce. In this study, selected yeasts were used to reduce the occurrence of deoxynivalenol (DON), nivalenol (NIV), and zearalenone (ZEA) produced by Fusarium culmorum, F. graminearum, and F. poae on wheat grain and bread. In a laboratory experiment, an effective reduction in the content of DON, NIV, and ZEA was observed in bread prepared by baking with the addition of an inoculum of the test yeast, ranging from 16.4% to 33.4%, 18.5% to 36.2% and 14.3% to 35.4%, respectively. These results indicate that the selected yeast isolates can be used in practice as efficient mycotoxin decontamination agents in the food industry

Estimation of the Content of Selected Active Substances in Primary and Secondary Herbal Brews by UV-VIS and GC-MS Spectroscopic Analyses

Primary and secondary herbal brews were tested for the content of polyphenolic compounds, flavonoids, and essential oil. The brewing process was carried out at an initial temperature of 95°C and different time parameters (5, 10, 15, and 30 min). A secondary brewing was also carried out to estimate the reuse of the herbal material. The highest content of polyphenol compounds and flavonoids was determined in the primary peppermint brews (4017 mg L−1 and 360 mg L−1, respectively). The secondary brews were characterised by a lower content of active substances than the primary brews. The study showed that the herbal postbrewing material contained significant levels of essential oil (from 13.04% to 95.65%) and may be an alternative source of volatile bioactive compounds

Trudności w leczeniu chorego na ostrą białaczkę szpikową z mutacją FLT3-ITD i wysokim stosunkiem allelicznym — oporność na standardową chemioterapię indukującą w połączeniu z midostauryną

The development of targeted therapies in AML patients enabling treatment individualization, such as new FLT3 tyrosine kinase inhibitors, is a promising option for improving treatment outcomes and prolonging patient survival. However, the treatment of patients with a high FLT3-ITD allelic ratio (FLT3-ITDhigh) associated with an extremely unfavourable prognosis remains a major clinical problem. The study presents a case of a 20-year-old patient with FLT3-ITDhigh extramedullary AML at diagnosis. Individualized chemotherapy according to the DA ‘3 + 7’ regimen combined with midostaurin was administered. After the induction treatment, complete remission (CR) was not achieved. After second induction chemotherapy, CR1 was achieved with the presence of residua disease. One cycle of consolidation chemotherapy was then administered, and after myeloablative conditioning allogeneic hematopoietic stem cell transplantation from an unrelated donor was performed. The patient has remained in CR with no residual disease for 18 months.  Rozwój terapii celowanych u chorych na AML, umożliwiających indywidualizację leczenia, w tym zastosowanie nowych inhibitorów kinaz tyrozynowych FLT3, jest obiecującą perspektywą dla poprawy wyników leczenia i wydłużenia czasu przeżycia chorych. Jednakże problemem pozostaje leczenie chorych z obecnością wysokiego stosunku allelicznego FLT3 — FLT3-ITDhigh — związanego z wyjątkowo niekorzystnym rokowaniem. W pracy przedstawiono przypadek 20-letniego chorego na AML z obecnością FLT3-ITDhigh z lokalizacjami pozaszpikowymi AML przy rozpoznaniu. Leczenie chorego zindywidualizowano, stosując chemioterapię indukującą skojarzoną z midostauryną. Po zastosowaniu leczenia indukującego według schematu DA „3 + 7” nie osiągnięto u chorego całkowitej remisji (CR). Po włączeniu drugiej chemioterapii indukującej uzyskano CR z obecnością choroby resztkowej. Następnie podano jeden cykl chemioterapii konsolidującej oraz, po zastosowaniu kondycjonowania mieloablacyjnego, przeprowadzono przeszczepienie allogenicznych krwiotwórczych komórek macierzystych od dawcy niespokrewnionego. Pacjent pozostaje w CR bez obecności choroby resztkowej od 18 miesięcy

Applications of Adductomics in Chemically Induced Adverse Outcomes and Major Emphasis on DNA Adductomics: A Pathbreaking Tool in Biomedical Research

Adductomics novel and emerging discipline in the toxicological research emphasizes on adducts formed by reactive chemical agents with biological molecules in living organisms. Development in analytical methods propelled the application and utility of adductomics in interdisciplinary sciences. This review endeavors to add a new dimension where comprehensive insights into diverse applications of adductomics in addressing some of society’s pressing challenges are provided. Also focuses on diverse applications of adductomics include: forecasting risk of chronic diseases triggered by reactive agents and predicting carcinogenesis induced by tobacco smoking; assessing chemical agents’ toxicity and supplementing genotoxicity studies; designing personalized medication and precision treatment in cancer chemotherapy; appraising environmental quality or extent of pollution using biological systems; crafting tools and techniques for diagnosis of diseases and detecting food contaminants; furnishing exposure profile of the individual to electrophiles; and assisting regulatory agencies in risk assessment of reactive chemical agents. Characterizing adducts that are present in extremely low concentrations is an exigent task and more over absence of dedicated database to identify adducts is further exacerbating the problem of adduct diagnosis. In addition, there is scope of improvement in sample preparation methods and data processing software and algorithms for accurate assessment of adducts