The effects of quercetin vs cisplatin on proliferation and the apoptotic process in A549 and SW1271 cell lines in in vitro conditions

Experience over several years has indicated that chemotherapy, even if widely used, does not always remain effective in the therapy of lung tumours and, in addition, is linked to serious side effects. In parallel, some plant polyphenols are known to exert a proapoptotic action on tumour cells while, in contrast, representing anti-cancerogenic anti-oxidants in living organisms. Our studies were aimed at comparing the effects of a polyphenol, quercetin, and cisplatin on cells of various types of lung cancer in in vitro conditions. In these studies we also attempted to define the relationship between the dose and the duration of the activity of the compounds. Cisplatin alone was found to induce only a small reaction in the cells, while in combination with quercetin its anti-proliferative and pro-apoptotic effects were amplified, depending upon the type of tumour, the dose and the duration of the drug’s action

Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.

Polyphenols are present in several edible plants and for many years induce high interest mainly due to their antioxidative and anti-inflammatory influence. At present, numerous studies are conducted on antineoplastic effects of the compounds. One of most effective biopolyphenols involves the flavonol quercetin. Our studies aimed at evaluation of antiproliferative and pro-apoptotic effects of quercetin alone and in combinations with daunorubicin on cells of human pancreatic carcinoma lines. The experiments were conducted on two cell lines, sensitive to daunorubicin EPP85-181P line, and its resistant variant EPP85-181RDB. Effect of studied substances on cell proliferation was detected using sulphorhodamine B (SRB) protein staining method. Apoptotic damage was estimated using comet and TUNEL techniques. Our data demonstrated that quercetin exerted cytotoxic action on cells of the both neoplastic cell lines in concentration-dependent manner. In the case of EPP85-181RDB cell line, quercetin seemed to sensitize resistant cells to daunorubicin. In parallel, the effect of both substances on the sensitive cell line was synergistic. Results of the studies confirmed that quercetin may probably break resistance of neoplastic cells to chemotherapy. On the other side, studied flavonol augmented action of cytostatic drug in case of sensitive tumour cells what suggest, that it might allow to decrease dosage of cytostatic drugs and reduce negative side effects of the treatment

Role of Lipid Peroxidation Products, Plasma Total Antioxidant Status, and Cu-, Zn-Superoxide Dismutase Activity as Biomarkers of Oxidative Stress in Elderly Prediabetics

The relationship between hyperglycemia and oxidative stress in diabetes is well known, but the influence of metabolic disturbances recognized as prediabetes, in elderly patients especially, awaits for an explanation. Methods. 52 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), body mass index (BMI), percentage of body fat (FAT), and arterial blood pressure. During an oral glucose tolerance test (OGTT) fasting (0′) and 120-minute (120′) glycemia and insulinemia were determined, and type 2 diabetics (n=6) were excluded. Subjects were tested for glycated hemoglobin HbA1c, plasma lipids, total antioxidant status (TAS), thiobarbituric acid-reacting substances (TBARS), and activity of erythrocyte superoxide dismutase (SOD-1). According to OGTT results, patients were classified as normoglycemics, (NGT, n=18) and prediabetics, (PRE, n=28). Results. Both groups did not differ with their lipids, FAT, and TBARS. PRE group had higher WC (P<0.002) and BMI (P<0.002). Lower SOD-1 activity (P<0.04) and TAS status (P<0.04) were found in PRE versus NGT group. Significance. In elderly prediabetics, SOD-1 and TAS seem to reflect the first symptoms of oxidative stress, while TBARS are later biomarkers of oxidative stress

An open multicentre trial to study the efficacy and safety of human insulin Gensulin in patients with type 1 and 2 diabetes mellitus : assumptions and preliminary results at 28 weeks

WSTĘP. Wieloletnie badania prospektywne dostarczyły dowodów na znaczenie dobrego wyrównania cukrzycy w zapobieganiu przewlekłym powikłaniom i hamowaniu ich progresji. Dobre wyrównanie cukrzycy można uzyskać dzięki insulinom ludzkim syntetyzowanym na podstawie techniki rekombinacji DNA. Gensulin jest pierwszym polskim preparatem rekombinowanej insuliny ludzkiej. CELE. 1. Ocena skuteczności insuliny Gensulin na podstawie badania wpływu leczenia na wyrównanie cukrzycy określane na podstawie dobowego profilu glikemii i stężenia hemoglobiny glikowanej (HbA1c). 2. Ocena bezpieczeństwa leku na podstawie badania wpływu terapii na epizody hipoglikemii, weryfikacji parametrów funkcji układu krążenia, wątroby i nerek oraz oceny immunogenności insuliny. 3. Ocena wpływu leczenia na jakość życia dokonana na podstawie wypełnianego przez chorych kwestionariusza. MATERIAŁ I METODY. Badanie otwarte IV fazy docelowo obejmie 60 chorych na cukrzycę typu 1 (DMT1, type 1 diabetes mellitus) i na cukrzycę typu 2 (DMT2, type 2 diabetes mellitus) w okresie 52 tygodni. Obecna wstępna analiza dotyczy 25 chorych - 13 chorych na DMT1 i 12 chorych z DMT2, którzy odbyli wizytę W8, to znaczy przez 28 tygodni otrzymywali Gensulin. Pacjenci z DMT1 otrzymywali Gensulin R i N w modelu 4–5 wstrzyknięć (IT, intensive therapy), chorych z DMT2 leczono modelem IT lub 2 wtrzyknięciami mieszanek Gensulin R i N. WYNIKI I WNIOSKI. W ciągu 28 tygodni stosowania insuliny Gensulin u chorych na cukrzycę typu 1 i 2 nie stwierdzono istotnych różnic w wyrównaniu cukrzycy, które oceniano na podstawie stężenia HbA1c (odpowiednio: wizyta 1 — 7,6 ± 0,7%/wizyta 8 — 7,5 ± 0,9% w DMT1 i 6,9 ± 0,8%/7,0 ± 0,8% w DMT2). Zarówno u chorych na DMT1, jak i DMT2 stwierdzono istotne statystycznie zmniejszenie dobowych wahań glikemii mierzonych odchyleniem standardowym od średniej glikemii (odpowiednio DMT1: wizyta 1 — 46,3 ± 20,4 mg/dl/wizyta 7 — 34,4 ± 12,8 mg/dl i DMT2: wizyta 1 — 34,9 ± 14,2 mg/dl/wizyta 8 — 20,3 ± 6,6 mg/dl). W obu typach cukrzycy stwierdzono poprawę kontroli glikemii mierzoną wskaźnikiem J. Częstość hipoglikemii podczas leczenia preparatem Gensulin odpowiadała częstości podczas stosowania innych preparatów insuliny (DMT1 — 1,19/osobomiesiąc, DMT2 — 0,13/osobomiesiąc). Insulina Gensulin wykazuje zbliżone cechy kliniczne do innych preparatów insulin ludzkich.INTRODUCTION. Long-term multicentre prospective studies provided evidence for the value of good diabetes control in the prevention of complications and inhibition of their progression. Adequate diabetes control can be achieved with human insulin synthesised by DNA recombination technique. Gensulin is the first Polish recombinant human insulin. AIM. 1. To evaluate the efficacy of Gensulin based upon the effect of treatment on diabetes control measured by 24 hr glycemia and HbA1c levels. 2. To evaluate the safety of Gensulin based upon the effect of treatment on the occurrence of hypoglycemia, cardiovascular function, liver and kidney function and insulin immunogenicity. 3. To evaluate the effect of Gensulin on the quality of life based upon a questionnaire. MATERIAL AND METHODS. It is an open phase IV study designed to recruit 60 patients with DMT1 and DMT2 within 52 weeks. The present preliminary analysis was carried out in 25 patients - 13 with DMT1 and 12 with DMT2, who completed visit 8 i.e. had been receiving Gensulin for 28 weeks. Patients with DMT1 were receiving Gensulin R and N in 4–5 injections (IT), patients with DMT2 were given the IT model or 2 injections of Gensulin R and N. RESULTS AND CONCLUSIONS. Within the first 28 weeks on Gensulin treatment there were no significant differences in diabetes control measured by HbA1c (visit 1 —7.6 ± 0.7%/visit 8 — 7.5 ± 0.9% in DMT1 and 6.9 ± 0.8%/7.0 ± 0.8% in DMT2). In both groups daily variations in glycemia measured by standard deviation of the mean glycemia were significantly lower (DMT1: visit 1 — 46.3 ± 20.4 mg/dl/visit 7 — 34.4 ± 12.8 mg/dl and DMT2: visit 1 — 34.9 ± 14.2 mg/dl/visit 8 — 20.3 ± 6.6 mg/dl). In both types of diabetes glycemia control measured by J index was improved. The frequency of hypoglycemia corresponded to that during treatment with other insulin preparations (DMT1 — 1.19/personmonth, DMT2 — 0.13/personmonth). Gensulin has similar clinical properties to other human insulin preparations

An open multicentre trial to study the efficacy and safety of human insulin Gensulin in patients with type 1 and 2 diabetes mellitus &#8212; assumptions and preliminary results at 28 weeks

WSTĘP. Wieloletnie badania prospektywne dostarczyły dowodów na znaczenie dobrego wyrównania cukrzycy w zapobieganiu przewlekłym powikłaniom i hamowaniu ich progresji. Dobre wyrównanie cukrzycy można uzyskać dzięki insulinom ludzkim syntetyzowanym na podstawie techniki rekombinacji DNA. Gensulin jest pierwszym polskim preparatem rekombinowanej insuliny ludzkiej. CELE. 1. Ocena skuteczności insuliny Gensulin na podstawie badania wpływu leczenia na wyrównanie cukrzycy określane na podstawie dobowego profilu glikemii i stężenia hemoglobiny glikowanej (HbA1c). 2. Ocena bezpieczeństwa leku na podstawie badania wpływu terapii na epizody hipoglikemii, weryfikacji parametrów funkcji układu krążenia, wątroby i nerek oraz oceny immunogenności insuliny. 3. Ocena wpływu leczenia na jakość życia dokonana na podstawie wypełnianego przez chorych kwestionariusza. MATERIAŁ I METODY. Badanie otwarte IV fazy docelowo obejmie 60 chorych na cukrzycę typu 1 (DMT1, type 1 diabetes mellitus) i na cukrzycę typu 2 (DMT2, type 2 diabetes mellitus) w okresie 52 tygodni. Obecna wstępna analiza dotyczy 25 chorych &#8212; 13 chorych na DMT1 i 12 chorych z DMT2, którzy odbyli wizytę W8, to znaczy przez 28 tygodni otrzymywali Gensulin. Pacjenci z DMT1 otrzymywali Gensulin R i N w modelu 4-5 wstrzyknięć (IT, intensive therapy), chorych z DMT2 leczono modelem IT lub 2 wtrzyknięciami mieszanek Gensulin R i N. WYNIKI I WNIOSKI. W ciągu 28 tygodni stosowania insuliny Gensulin u chorych na cukrzycę typu 1 i 2 nie stwierdzono istotnych różnic w wyrównaniu cukrzycy, które oceniano na podstawie stężenia (HbA1c)(odpowiednio: wizyta 1 &#8212; 7,6 &plusmn; 0,7%/wizyta 8 &#8212; 7,5 &plusmn; 0,9% w DMT1 i 6,9 &plusmn; 0,8%/7,0 &plusmn; 0,8% w DMT2). Zarówno u chorych na DMT1, jak i DMT2 stwierdzono istotne statystycznie zmniejszenie dobowych wahań glikemii mierzonych odchyleniem standardowym od średniej glikemii (odpowiednio DMT1: wizyta 1 &#8212; 46,3 &plusmn; 20,4 mg/dl/wizyta 7 &#8212; 34,4 &plusmn; 12,8 mg/dl i DMT2: wizyta 1 &#8212; 34,9 &plusmn; 14,2 mg/dl/wizyta 8 &#8212; 20,3 &plusmn; 6,6 mg/dl). W obu typach cukrzycy stwierdzono poprawę kontroli glikemii mierzoną wskaźnikiem J. Częstość hipoglikemii podczas leczenia preparatem Gensulin odpowiadała częstości podczas stosowania innych preparatów insuliny (DMT1 &#8212; 1,19/osobomiesiąc, DMT2 &#8212; 0,13/osobomiesiąc). Insulina Gensulin wykazuje zbliżone cechy kliniczne do innych preparatów insulin ludzkich.INTRODUCTION. Long-term multicentre prospective studies provided evidence for the value of good diabetes control in the prevention of complications and inhibition of their progression. Adequate diabetes control can be achieved with human insulin synthesised by DNA recombination technique. Gensulin is the first Polish recombinant human insulin. AIM. 1. To evaluate the efficacy of Gensulin based upon the effect of treatment on diabetes control measured by 24 hr glycemia and HbA1c levels. 2. To evaluate the safety of Gensulin based upon the effect of treatment on the occurrence of hypoglycemia, cardiovascular function, liver and kidney function and insulin immunogenicity. 3. To evaluate the effect of Gensulin on the quality of life based upon a questionnaire. MATERIAL AND METHODS. It is an open phase IV study designed to recruit 60 patients with DMT1 and DMT2 within 52 weeks. The present preliminary analysis was carried out in 25 patients &#8212; 13 with DMT1 and 12 with DMT2, who completed visit 8 i.e. had been receiving Gensulin for 28 weeks. Patients with DMT1 were receiving Gensulin R and N in 4&#8211;5 injections (IT), patients with DMT2 were given the IT model or 2 injections of Gensulin R and N. RESULTS AND CONCLUSIONS. Within the first 28 weeks on Gensulin treatment there were no significant differences in diabetes control measured by HbA1c (visit 1 &#8212; 7.6 &plusmn; 0.7%/visit 8 &#8212; 7.5 &plusmn; 0.9% in DMT1 and 6.9 &plusmn; 0.8%/7.0 &plusmn; 0.8% in DMT2). In both groups daily variations in glycemia measured by standard deviation of the mean glycemia were significantly lower (DMT1: visit 1 &#8212; 46.3 &plusmn; 20.4 mg/dl/visit 7 &#8212; 34.4 &plusmn; 12.8 mg/dl and DMT2: visit 1 &#8212; 34.9 &plusmn; 14.2 mg/dl/visit 8 &#8212; 20.3 &plusmn; 6.6 mg/dl). In both types of diabetes glycemia control measured by J index was improved. The frequency of hypoglycemia corresponded to that during treatment with other insulin preparations (DMT1 &#8212; 1.19/personmonth, DMT2 &#8212; 0.13/personmonth). Gensulin has similar clinical properties to other human insulin preparations

Poland, Slovenia, the World : Challenges of present-day education

Publikacja recenzowana / Peer-reviewed publicationTransformations of education in changing Europe are multifaceted. One of the latter is the process of strengthening the cooperation among universities in this part of the world. This cooperation is carried out in many fields – from joint projects and researches – to joint analyses, discourses and publications. This monograph – a collection of reflections, thoughts and polemics deriving from theoretical and empirical researches, carried out as a part of a joint research project simultaneously undertaken at both these universities under the name “Problems and challenges of modern education” – constitutes one of the fruits of the cooperation between Andrzej Frycz Modrzewski Cracow University and the University of Ljubljana

Establishment of Histone Modifications after Chromatin Assembly

Every cell has to duplicate its entire genome during S-phase of the cell cycle. After replication, the newly synthesized DNA is rapidly assembled into chromatin. The newly assembled chromatin ‘matures’ and adopts a variety of different conformations. This differential packaging of DNA plays an important role for the maintenance of gene expression patterns and has to be reliably copied in each cell division. Posttranslational histone modifications are prime candidates for the regulation of the chromatin structure. In order to understand the maintenance of chromatin structures, it is crucial to understand the replication of histone modification patterns. To study the kinetics of histone modifications in vivo, we have pulse-labeled synchronized cells with an isotopically labeled arginine (15N4) that is 4 Da heavier than the naturally occurring 14N4 isoform. As most of the histone synthesis is coupled with replication, the cells were arrested at the G1/S boundary, released into S-phase and simultaneously incubated in the medium containing heavy arginine, thus labeling all newly synthesized proteins. This method allows a comparison of modification patterns on parental versus newly deposited histones. Experiments using various pulse/chase times show that particular modifications have considerably different kinetics until they have acquired a modification pattern indistinguishable from the parental histones