Bortezomib in the first-line treatment of patients with plasma cell myeloma and renal failure

W pracy przedstawiono opis leczenia 2 chorych z rozpoznaniem szpiczaka plazmocytowego (PCM) z towarzyszącą niewydolnością nerek, u których w I linii leczenia zastosowano schematy chemioterapii oparte na bortezomibie. Szpiczak plazmocytowy jest chorobą nowotworową charakteryzującą się monoklonalnym rozrostem komórek plazmatycznych, nadal nieuleczalną. Jednym z najpoważniejszych problemów w przebiegu PCM pozostaje uszkodzenie nerek, które występuje u 20–25% chorych z nowo rozpoznanym PCM i u 50% pacjentów z chorobą nawrotową/oporną na leczenie. Wprowadzenie do leczenia nowych leków, w tym bortezomibu, pozwoliło na uzyskanie odpowiedzi terapeutycznej u większości chorych. Zastosowanie bortezomibu w I linii leczenia, w skojarzeniu z deksametazonem i innymi cytostatykami, daje szansę na uzyskanie odpowiedzi na leczenie u 80–90% chorych. Przedstawione w pracy przypadki dowodzą skuteczności i bezpieczeństwa bortezomibu w leczeniu chorych na PCM i niewydolność nerek.In the present paper we describe 2 cases of plasma cell myeloma (PCM) and renal insufficiency to whom bortezomid was administred as first-line treatment. Plasma cell myeloma is a malignant disease characterised by excessive proliferation of monoclonal plasmacytic cells. It is still considered as an uncurable disease. One of the severest problems in the course of this disease is the renal failure, which occurs in 20–25% of newly diagnosed patients and 50% of those having the relapsed/refractory disease. Introduction of the novel drugs such as bortezomib into the therapy of PCM, allowed to obtain a response to treatment in the majority of patients. Administration of bortezomib to the first-line treatment in association with dexamethasone and other cytostatics may result in response in 80–90% patients. Presented cases proof the efficacy and safety of bortezomib in treatment of patients with PCM and renal failure

Efficacy of rituximab in refractory primary immune thrombocytopenia

W pracy przedstawiono opis przypadku skutecznego zastosowania rytuksymabu w opornej na leczenie pierwotnej małopłytkowości immunologicznej (ITP). Mimo początkowej odpowiedzi na leczenie kortykosteroidami u większości dorosłych z ITP dochodzi do nawrotu choroby przy próbie zmniejszenia dawki leków. Osoby te są kandydatami do zabiegu usunięcia śledziony. Wyzwaniem są pacjenci, u których nie powiodła się splenektomia. Kolejne linie leczenia obejmują różne formy immunosupresji, obciążone jednak licznymi działaniami niepożądanymi. W niniejszej pracy przedstawiono przypadek opornej na leczenie ITP u pacjentki, u której uzyskano zwiększenie liczby płytek krwi, a następnie remisję choroby po zastosowaniu rytuksymabu. Hematologia 2011; 2, 1: 88–91This paper presents the case report of efficient use of rituximab in the treatment of refractory primary immune thrombocytopenia (ITP). Despite initial response to corticosteroids, most adults relapse during corticosteroid taper. Splenectomy should be taken into consideration in such situations. Those whom splenectomy fails to cure present a therapeutic challenge. Subsequent management usually involves some form of chronic immune suppression which, however, has serious side effects. The case of patient with refractory ITP, who achieved increased platelet counts and then the remission of disease after treatment with rituximab, is discussed in this paper. Hematologia 2011; 2, 1: 88–9

Multimedia w edukacji. Potencjał audiodeskrypcji w kierowaniu uwagą wzrokową ucznia

Multimedia in Education: AD Potential in Guiding the Learner’s Visual Attention The aim of this article is to present audio description as a technique of subtle gaze direction during the perception of multimedia material. Multimedia educational materials dynamically take over the educational market. Substantial research findings support their effectiveness; however, there are also arguments pointing at difficulties in the perception of multimedia materials. In this paper we focus on two potential sources of these problems. The first source we associate with the design of multimedia. There are a number of rules that need to be followed when designing multimedia educational materials, such as the rule of multimodality or the rule of time and space coherence. The second source of the diffi culties we assign to the complexity of multimedia which may result in cognitive overload. As a solution we postulate to introduce audio description as a technique leading to the unity of image and sound. Supporting arguments come from eye-tracking studies on audio description in the education of sighted people. For example, primary school children watching a film with audio description concentrated their gaze more on the object highlighted in audio description than the control group what helps in the learning content understanding. The research overview positively verifies the potential role of audio description as a subtle gaze direction in the multimedia education of sighted people

The influence of structural and functional changes on N-P-K input of agricultural origin and surface water quality in the upper Dunajec River basin in the years 1980–2010

The aim of the study was the prediction of N-P-K inputs (hereafter referred to as NPK load) from agricultural sources. The study aimed to determine relations between the structural changes and the N-P-K load (nitrogen-phosphorus-potassium) fertilizer components in the upper Dunajec River basin (the Carpathian region in Poland). Analysis included the level and nature of agricultural production, the land use structure and non-agricultural factors. Multiple regression analysis was used for the development of the model. Relationships were determined in the form of regression models in the system of N-P-K load-structural parameters-land use-surface water quality. The quality of surface water was assessed in a range of concentrations of N-NO3-, N-NH4+, PO43-, Cl-, and compared to the N-P-K load that was brought to the basin from agricultural sources. Significant structural and spatial changes took place in the upper Dunajec River basin that affected many social, economic and environmental factors. Agricultural production was reduced, resulting in a decrease of area of agricultural land between the year 1980 and 2010. The most important factors influencing the changes in biogenic load of an agricultural origin were: stocking density and mineral fertilization. Both of these parameters determined the amount of N-P-K load in approx. 80-90% (not counting the use of N-P-K components by crops). Surface water quality has generally improved, only higher concentrations of chlorides were recorded in small urbanized river basins. Therefore, the chemical composition of water plays the role of a simplified indicator of structural changes. Mathematical formulas proved changes in N-P-K load depending on variations of individual influencing factors. The development of the usable space of the investigated river basin must take into account agricultural and non-agricultural factors, as well as the proportions and relationships between them. Only then might the sustainable and multifunctional development of these areas be provided

Modelling of long term low water level in mountain river catchments area

Changing atmospheric conditions, including above all the deepening extreme weather phenomena, are increasing from year to year. This, in consequence, causes an increase in the incidence of low outflows. The study compares low water levels for two catchments: Biała Woda and Czarna Woda, and phosphorus and nitrogen load using the Nutrient Delivery Ratio (NDR) model in InVEST software. The objective of the NDR is to map nutrient sources from catchment area and transfer to the river bed. The nutrient loads (nitrogen and phosphorus) spread across the landscape are determined based on a land use (LULC) map and associated loading rates described in literature. The studies have shown that low water levels have been more common recently and pose the greatest threat to the biological life in the aquatic ecosystems. The structure of land use is also of great importance, with a significant impact on the runoff and nitrogen and phosphorus load. Phosphorus and runoff from surface sources to the water of Biała Woda and Czarna Woda catchments area has been reduced in forested areas. Only higher run-offs are observed in the residential buildings zone. The nitrogen load was also greater in the lower (estuary) parts of both catchments, where residential buildings dominate.info:eu-repo/semantics/publishedVersio

The leaching of mineral nitrogen forms from light soil fertilized with compost and sewage sludge

The research was carried out in the years 2003-2013 in lysimeters filled with loamy sand. The leachate was tested in three variants: Z - no fertilization, S - 20 g-m-2 of N delivered annually in sewage sludge and C - 20 g-m-2 of N in the form of compost. The lysimeters were planted with Miscanthus giganteus, which is an energy plant with a high demand for water and nutrients. The amount of leaching of mineral nitrogen forms was determined on the basis of measured volumes of leachates from the soil and volumes of ammonium nitrogen (N-NH4) and nitrate nitrogen (N-NO3) contained in them. The research results showed a significant increase in the average content of mineral nitrogen forms in the effluents from the fertilized soil (S - 6.8 mg-dm-3 of N-NO3 and 0.3 mg-dm-3 of N-NH4, C - 7.8 mg-dm-3 of N-NO3 and 0.4 mg-dm-3 of N-NH4), compared to their concentrations in the leachates from non-fertilized soil (Z - 2.1 mg-dm-3 of N-NO3 and 0.2 mg-dm-3 of N-NH4). The content of mineral forms of nitrogen, in particular N-NO3, were similar in both fertilization variants. The lowest concentrations of mineral nitrogen in the leachates occurred in the third and fourth year after planting Miscanthus giganteus, when it entered the period of the highest yield. In the fifth year, due to a cold, snowless winter, there was a weakened growth of plants, which resulted in an increase in the concentration of mineral nitrogen in the leachates from the fertilized soil. It follows that in addition to the intensity of precipitation, the collection of this component by plants primarily influences nitrogen leaching from the soil. The general amount of mineral nitrogen leached from the soil was not large and amounted Z - 2.5 kg-m-2, S - 6.7 kg-m-2, C - 6.4 kg-m-2. This testifies to the intense collection of this form of nitrogen by Miscanthus giganteus

Casein kinase 2 activity is a host restriction factor for AAV transduction

So far, the mechanisms that impede AAV transduction, especially in the human heart, are poorly understood, hampering the introduction of new, effective gene therapy strategies. Therefore, the aim of this study was to identify and overcome the main cellular barriers to successful transduction in the heart, using iPSC-derived cardiomyocytes (iPSC-CMs), cardiac fibroblasts (iPSC-CFs), and primary endothelial cells (HAECs) to model vector-host interactions. Through phosphoproteome analysis we established that casein kinase 2 (CK2) signalling is one of the most significantly affected pathways upon AAV exposure. Transient inhibition of CK2 activity substantially enhanced the transduction rate of AAV2, AAV6 and AAV9 in all tested cell types. In particular, CK2 inhibition improved the trafficking of AAVs through the cytoplasm, impaired DNA-damage response through destabilisation of Mre11 and altered the RNA processing pathways, which were also highly responsive to AAV transduction. Also, it augmented transgene expression in already transduced iPSC-CFs, which retain AAV genomes in a functional, but probably silent form. In summary, presented study provides new insights into the current understanding of the host-AAV vector interaction, identifying CK2 activity as a key barrier to efficient transduction and transgene expression, what may translate to improvement the outcome of AAV-based therapies in the future

Cukrzyca w okresie niemowlęcym — trudności diagnostyczno-terapeutyczne

Etiologia cukrzycy w okresie noworodkowym jest przedmiotem licznych badań. Często objawy cukrzycy w wieku noworodkowym i niemowlęcym są niecharakter ystyczne, a rozpoznanie choroby stawiane późno. Dzieci z utrwaloną cukrzycą noworodkową charakteryzują się niską masą urodzeniową, znaczną hiperglikemią, często ze współistniejącą kwasicą metaboliczną. Stwierdzenie hiperglikemii w okresie noworodkowym wymaga natychmiastowego wdrożenia insulinoterapii, która jest niezbędnado prawidłowego rozwoju dziecka. W pracy przedstawiono trudności diagnostyczno-terapeutyczne u 30-dniowego dziecka zanim doszło do ostatecznego rozpoznania choroby — przetrwałej cukrzycy noworodkowej

Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency

Kidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of hypertension with angiotensin II (Ang II) combined with simvastatin administration results in a high mortality rate or the appearance of signs of kidney failure in heme oxygenase-1 knockout (HO-1 KO) mice. Here, we aimed to address the mechanisms underlying this effect, focusing on heme and iron metabolism. We show that HO-1 deficiency leads to iron accumulation in the renal cortex. Higher mortality of Ang II and simvastatin-treated HO-1 KO mice coincides with increased iron accumulation and the upregulation of mucin-1 in the proximal convoluted tubules. In vitro studies showed that mucin-1 hampers heme- and iron-related oxidative stress through the sialic acid residues. In parallel, knock-down of HO-1 induces the glutathione pathway in an NRF2-depedent manner, which likely protects against heme-induced toxicity. To sum up, we showed that heme degradation during heme overload is not solely dependent on HO-1 enzymatic activity, but can be modulated by the glutathione pathway. We also identified mucin-1 as a novel redox regulator. The results suggest that hypertensive patients with less active HMOX1 alleles may be at higher risk of kidney injury after statin treatment