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Leczenie przewlekłej białaczki limfocytowej (PBL) – - od przeszłości do teraźniejszości

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Gumieniczek A., Ciseł B., Lipska K., Filip A. A.
Farmacja Polska
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2020
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vol. 76
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issue 1
47-56
EN
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Western European countries. This disease occurs mainly in adult population at an age of over 50 years, more commonly in men. Many years of research have shown that CLL is a disease with a very diverse clinical course and variable sensitivity to treatment. Therefore, in each case of newly diagnosed CLL, the clinical stage, prognostic factors and individualized therapeutic goals should be precisely defined before the treatment initiation. Recent 50 years have been a period of significant development in the treatment of proliferative diseases of the hematopoietic and lymphatic systems. Along with dynamic development of molecular biology techniques, several new specific prognostic markers have been investigated and introduced, allowing better stratification of patients and more accurate direction of the therapy. A lot of effort has gone into searching for the next prognostic factors which allow to determine better probable life span and to implement the successful treatment. Furthermore, many preclinical and clinical studies continually extend the list of effective anticancer drugs, including these for CLL treatment. Increasingly, in addition to standard cytostatics, drugs with more selective mechanisms of action are being tested in monotherapy and new combinations. Considering the historical aspects, only a few anticancer drugs were available 50 years ago. In addition, they mainly presented the one mechanism of action directed at nucleic acids. Today, the list of effective drugs is significantly longer. In addition to typical cytostatics, it also contains drugs with selective mechanisms of action, affecting the cell life processes, their subcellular structures, signaling from outside and inside the cell, surface antigens, as well as drugs that act on the microenvironment of cancer cells and their vascularization. The aim of this paper was to show the historical background in the therapy of leukemia and summarize the current knowledge in CLL biology and treatments. The manuscript is focused on the clinical course of the disease, the main risk factors and mainly, on the available treatment strategies.
PL
Przewlekła białaczka limfocytowa (PBL) jest najczęściej występującą postacią białaczki w krajach Europy Zachodniej. Jest to choroba dotycząca przede wszystkim osób powyżej 50 roku życia, częściej mężczyzn niż kobiet. Wieloletnie badania wykazały, że PBL jest chorobą o bardzo zróżnicowanym przebiegu klinicznym i zmiennej wrażliwości na zastosowane leczenie. W związku z powyższym, w każdym przypadku nowo zdiagnozowanej PBL, przed rozpoczęciem leczenia, należy precyzyjnie określić stadium zaawansowania klinicznego, czynniki prognostyczne oraz cele terapeutyczne zindywidualizowane dla danego pacjenta. Ostatnie 50 lat to okres istotnego postępu w leczeniu chorób rozrostowych układu krwiotwórczego i chłonnego. Wraz z dynamicznym rozwojem technik biologii molekularnej pojawiły się nowe, specyficzne czynniki prognostyczne, umożliwiające lepszą stratyfikację chorych oraz dokładniejsze określenie dalszego kierunku terapii. W dalszym ciągu prowadzone są prace nad kolejnymi czynnikami umożliwiającymi określenie długości przeżycia pacjenta oraz szans powodzenia terapii. Jednocześnie prowadzone badania przedkliniczne i kliniczne wydłużają listę bardziej skutecznych leków przeciwnowotworowych, znajdujących swoje zastosowanie również w PBL. Coraz częściej obok standardowych cytostatyków pojawiają się leki o bardziej swoistym mechanizmie działania, zarówno w monoterapii, jak i w nowych połączeniach. Celem pracy było przedstawienie rysu historycznego w zakresie terapii białaczek i przegląd dotychczasowej wiedzy na temat charakterystyki i terapii PBL. W artykule zwrócono szczególną uwagę na przebieg choroby, czynniki ryzyka oraz stosowane obecnie strategie leczenia.
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Changes in antioxidant status of heart muscle tissue in experimental diabetes in rabbits.

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Gumieniczek A., Hopkała H., Wójtowicz Z., Nikołajuk J.
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2002
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vol. 49
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issue 2
529-535
EN
The present study was designed to evaluate the oxidative stress-related parameters in alloxan-induced diabetes in rabbits. After 3, 6, 12 and 24 weeks of hyperglycaemia the enzymatic and non-enzymatic factors were measured in heart tissue of diabetic and control groups. Superoxide dismutase and glutathione peroxidase activities and the contents of total sulfhydryl compounds significantly increased at all time intervals. Catalase activity increased initially (after 3 and 6 weeks), decreased after 12 weeks and increased again at the 24th week of the experiment. Glutathione reductase activity increased initially (at 3rd week), decreased below control level after 6 and 12 weeks, then increased again. Ascorbic acid concentration decreased after 3 and 6 weeks, and increased at the 12th and 24th weeks. The level of lipid peroxidation products was reduced after 3, 6 and 12 weeks of the experiment. After 24 weeks it was significantly elevated. These data suggest that hyperglycaemia induces oxidative stress in the heart but the defense mechanisms in the heart tissue are fairly efficacious against oxidative injury.
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Stress degradation study of two oral antidiabetics, gliclazide and glipizide, and chemical analysis by LC and LC/MS methods

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Gumieniczek A., Berecka A., Pietraś R., Ślebioda M.
Open Chemistry
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2014
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vol. 12
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issue 1
80-89
EN
Kinetic study of degradation of two oral antidiabetics, gliclazide and glipizide, was performed using new HPLC method which was validated in terms of selectivity, sensitivity, linearity, precision and accuracy. The stress degradation was performed in 0.2 M HCl, 0.2 M NaOH as well as in acetate and phosphate buffers over the pH range 3.8–8.3 at 30 and 70°C. In strong acidic and alkaline media gliclazide was almost fully degraded while glipizide showed much higher stability. Generally, degradation processes of gliclazide and glipizide were observed as the first order reactions while the rates of decomposition for both drugs were smallest at pH 8.3. The samples of gliclazide and glipizide stressed in strong acid and alkali at 70°C were additionally analyzed using an LC/MS method and some products of decomposition were detected and identified. It was concluded that glipizide was more resistant to very high or very low pH and would have higher stability compared to gliclazide. Such comparisons have not been performed so far for these valuable drugs. Additional LC/MS study showed that during decomposition of sulfonylureas, different degradation pathways were possible. [...]
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Zero crossing and ratio spectra derivative spectrophotometry for the dissolution tests of amlodipine and perindopril in their fixed dose formulations

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Maczka P., Gumieniczek A., Galeza J., Pietras R.
Current Issues in Pharmacy and Medical Sciences
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2014
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vol. 27
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issue 2
113-117
EN
Dissolution tests of amlodipine and perindopril from their fixed dose formulations were performed in 900 mL of phosphate buffer of pH 5.5 at 37°C using the paddle apparatus. Then, two simple and rapid derivative spectrophotometric methods were used for the quantitative measurements of amlodipine and perindopril. The first method was zero crossing first derivative spectrophotometry in which measuring of amplitudes at 253 nm for amlodipine and 229 nm for perindopril were used. The second method was ratio derivative spectrophotometry in which spectra of amlodipine over the linearity range were divided by one selected standard spectrum of perindopril and then amplitudes at 242 nm were measured. Similarly, spectra of perindopril were divided by one selected standard spectrum of amlodipine and then amplitudes at 298 nm were measured. Both of the methods were validated to meet official requirements and were demonstrated to be selective, precise and accurate. Since there is no official monograph for these drugs in binary formulations, the dissolution tests and quantification procedure presented here can be used as a quality control test for amlodipine and perindopril in respective dosage forms.
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A preliminary study on the effect of mineralization parameters on determination of metals in Viscum album species

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Blicharska E., Komsta Ł., Kocjan R., Gumieniczek A., Robak A.
Open Chemistry
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2010
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vol. 8
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issue 2
264-268
EN
An increasing interest in determination of various macro- and microelements in medicinal plants has been observed. The majority of studies are carried out using one mineralization method without any optimization. The present study demonstrates that changes in mineralization parameters can significantly affect the recovery of the elements determined. In the study, the dried plant material was mineralized in 12 ways and iron (Fe), copper (Cu), zinc (Zn), nickel (Ni) and manganese (Mn) levels were determined. The samples were mineralized in the dry or open microwave mode as well as 10 closed microwave modes. The influence of acid amounts, irradiation power and time, addition of hydrogen peroxide and perfluoric acid was examined. All parameters were shown to be critical - good efficiency was observed with larger amounts of acid. The determined content varied significantly in the same sample and were in the ranges (ug g−1): 46–136 (Fe), 1.4–11.8 (Cu), 4.0–11.3 (Ni), 15.4–53.8 (Zn) and 9.5–67.6 (Mn). Increased irradiation resulted in the loss of copper and zinc and better recovery of nickel. The results demonstrate that such determinations should include the mineralization optimization step. [...]
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New HPLC method for in vitro dissolution study of antihypertensive mixture amlodipine and perindopril using an experimental design

76%
Gumieniczek A., Mączka P., Inglot T., Pietraś R., Lewkut E., Perczak K.
Open Chemistry
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2013
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vol. 11
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issue 5
717-724
EN
A new HPLC method was developed for the determination of amlodipine and perindopril in their binary mixture as a part of a routine control of combined formulations. For the first time an HPLC method was used for an in vitro dissolution study of tablets containing the above drugs. The presented method was validated to meet official requirements and this validation included specificity, stability, linearity, precision and accuracy. Chromatography was carried out using a LiChrospher RP-18 column, a mixture containing acetonitrile and phosphate buffer of pH 3.0 (50:50, v/v) as mobile phase and UV detection at 225 nm. The dissolution test was performed using 900 mL of phosphate buffer at pH 5.5 containing 1% cetylpyridini chloride (CPC) at 37°C and 75 rpm, using the paddle method. Robustness procedure was done according to the plan defined by the Plackett-Burman design. The effects of acetonitrile content, pH of the buffer and flow rate of the mobile phase, column temperature, pH and CPC content in the dissolution medium as well as rotation speed of the paddle were considered. After that, both graphical and statistical methods were used for identification of significant and non-significant effects. [...]
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