Search results

1

The direction of the changes of rates of the internal and external training load under the influence of high-altitude hypoxia on mountain bikers

100%

Gabrys T., Szmatlan-Gabrys U., Stanula A.

Physical Activity Review

|

2019

|

issue 7

40-48

EN

The aim of the research carried out was to establish the direction, and scope of the changes in internal, and external load indicator values in cyclists, men, and women, in high-altitude hypoxia conditions. The participants of the study were mountain bike cyclists, members of Russian and Polish Nationals Teams (women n=11, men n=9). They have done the graded incremental exercise test at the altitude of 170 m (Lonato del Garda, Italy) and 2250 m (Livignio-Trepale Italy). In the course of effort VO2, VE, VCO2 was measured by means of K4b2 analyser (Cosmed Italy). Effort intensity was determined at ventilators thresholds VT1 (AT), and VT2. Internal and external load indicators undergo changes during physical effort in cyclists under the influence of high altitude hypoxia. In groups of men and women, the changes in indicator values reach VE: 9% and 12%, HR: 0,5% and 15, O2HR: 7% and 15%, VO2: 14% and 20% respectively, as well as a decrease in 5 and 4% of the generated power, respectively. A decrease in the generated power by 5%, higher ventilation, amounting to 10%, a higher VO2max, amounting to 17% in hypoxic conditions, in comparison with the conditions similar to those at sea level, show that it is necessary to modify training loads.

2

Properties of B16-F10 murine melanoma cells subjected to metabolic stress conditions

100%

Mitrus I., Bryndza E., Kazura M., Smagur A., Sochanik A., Cichon T., Szala S.

|

2012

|

vol. 59

|

issue 3

363-366

EN

Neoplastic cells which co-form tumors are usually subjected to various stress factors, mainly hypoxia and shortage of nutrient factors. Such cells employ different strategies that permit their survival under such conditions. Experiments in vitro are usually carried out in the presence of 21% oxygen and medium supplemented with 10% FBS. Altering these parameters can approximate the in vivo conditions found within tumor mass. The present paper reports certain properties (especially ability to metastasize) of B16-F10 cells able to grow upon exposure to altered growth conditions (medium supplemented with 0.06% FBS or presence of 1% oxygen for 24 or 72 hours). These properties were compared with those of control cells cultured in the presence of 21% oxygen and in medium supplemented with 10% FBS. Some properties of the cells exposed to medium supplemented with 0.06% FBS differ from those of cells cultured under low oxygenation conditions (ability to form metastases, to migrate, or to express various proteins). Only the partial deprivation of oxygen did increase both the number of migrating cells and the number of metastases formed. Serum deficiency enhanced only the cell ability to metastasize, but not to migrate. It appears that cultured B16-F10 cells employ different adaptation strategies under conditions of oxygen shortage and those of serum deficiency. Under oxygen deprivation, such cells most likely undergo an epithelial-mesenchymal transition, whereas serum deficiency ("starvation"), while increasing the tumorigenicity of B16-F10 cells, does not induce the epithelial-mesenchymal transition.

3

An Assessment of Exercise Tolerance in Normobaric Hypoxia of Patients with Diabetes Mellitus Type 1

100%

Głuchowska B., Żebrowska A., Kamiński T.

Human Movement

|

2014

|

vol. 15

|

issue 3

171-176

EN

Purpose. Physical activity is an integral part of the treatment of diabetes. The aim of the study was to assess aerobic capacity and cardiovascular-respiratory reactions to a single physical exercise with gradually increasing intensity in normobaric hypoxia in patients with Type 1 diabetes. Methods. The study was conducted on a sample of adults with Type 1 diabetes (GT1D, n = 13) and a randomly chosen healthy control (GK, n = 15). The study participants performed a progressive exercise test to exhaustion in normoxia (FiO2 ~ 20.90%) and 7 days later in normobaric hypoxia (FiO2 ~ 15.14%). At rest, during exercise, and after completion of the test blood was drawn and physiological indicators were monitored. Results. Two-way ANOVA revealed a significant effect of hypoxia and physical exercise on blood glucose concentrations (F = 6.1 p < 0.01). In GT1D , lower glucose levels were observed in normobaric hypoxia compared with baseline and post-exercise levels in normoxia (p < 0.05). A tendency to increased maximal oxygen uptake and significantly higher minute pulmonary ventilation was observed in both groups in response to exercise and hypoxia. Conclusions. Physical activity and hypoxia may effectively control glucose homeostasis and increase cardiorespiratory adaptation to exercise in Type 1 diabetics.

4

Influence of Hypoxia Training on the Aerobic Capacity of an Elite Race Walker

100%

Maciejczyk M., Sudoł G., Szyguła Z.

Human Movement

|

2012

|

vol. 13

|

issue 4

360-366

EN

Purpose. The aim of the study was to evaluate the influence of a combination of two different hypoxic training models (“live high-train high” and “live high-train low” with the use of a hypoxic tent) on the aerobic capacity of a elite race walker preparing for the 2009 IAAF World Championships. Methods. Evaluation of VO2max and the second ventilatory threshold was performed three times: 1) after four weeks training without hypoxic conditions, 2) after 28 days training in normoxia and sleeping for 8 h/day in a hypoxic tent (normobaric hypoxia, simulated hypoxia at 2133 m above sea level) and 3) after 26 days of classical altitude training at a moderate altitude of about 1800 m ASL (hypobaric hypoxia). The hematological parameters of the athlete’s blood (hematocrit, hemoglobin concentration, and erythrocytes and reticulocytes counts) were also measured after each stage. Results. After training in normoxia and sleeping in a hypoxic tent the ventilatory threshold was noted at a higher work intensity and featured an improvement in his hematological parameters, although VO2max was unchanged (compared to training without hypoxia). After classical altitude training a higher level of VO2max was observed (with a ventilatory threshold level similar to the level after training in normobaric hypoxia), but the hematological indices were lower than the levels observed before starting hypoxic training. Conclusions. The combination of two methods of hypoxic training improved the aerobic capacity of the test subject, but an improvement in the analyzed hematological indicators was observed only after LH + TL training. After training in LH + TH these indicators were lower in comparison to the levels prior hypoxic training. The changes in the hematological indices after hypoxic training did not seem to have a significant influence on aerobic capacity; the observed improvements in physical performance may result from other factors.

5

Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin

100%

Kocemba-Pilarczyk K., Ostrowska B., Trojan S., Aslan E., Kusior D., Lasota M., Lenouvel C., Dulińska-Litewka J.

|

2018

|

vol. 65

|

issue 1

101-109

EN

Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here.

6

Altitude Training and its Influence on Physical Endurance in Swimmers

100%

Strzała M., Ostrowski A., Szyguła Z.

Journal of Human Kinetics

|

2011

|

vol. 28

91-105

EN

It is possible to plan an altitude training (AT) period in such a way that the enhanced physical endurance obtained as a result of adaptation to hypoxia will appear and can be used to improve performance in competition. Yet finding rationales for usage of AT in highly trained swimmers is problematic. In practice AT, in its various forms, is still controversial, and an objective review of research concentrating on the advantages and disadvantages of AT has been presented in several scientific publications, including in no small part the observations of swimmers. The aim of this article is to review the various methods and present both the advantageous and unfavourable physiological changes that occur in athletes as a result of AT. Moreover, AT results in the sport of swimming have been collected. They include an approach towards primary models of altitude/hypoxic training: live high + train high, live high + train low, live low + train high, as well as subsequent methods: Intermittent Hypoxic Exposure (IHE) and Intermittent Hypoxic Training (IHT). Apnoea training, which is descended from freediving, is also mentioned, and which can be used with, or as a substitute for, the well-known IHE or IHT methods. In conclusion, swimmers who train using hypoxia may be among the best-trained athletes, and that even a slight improvement in physical endurance might result in the shortening of a swimming time in a given competition, and the achievement of a personal best, which is hard to obtain by normal training methods, when the personal results of the swimmer have reached a plateau.

7

Differential relationship between two hypoxia markers: HIF-1α and GLUT1 and classic prognostic factors in invasive breast carcinoma

88%

Żyromska A., Andrusewicz H., Łysik J., Jóźwicki W., Wiśniewski T.

Current Gynecologic Oncology

|

2016

|

vol. 14

|

issue 4

197-203

EN

Background: Tumor hypoxia is an adverse prognostic factor which promotes cancer aggressiveness and limits its radio- and chemosensitivity. The aim of our study was to explore the relationship between endogenous hypoxia markers and classic prognostic factors, including clinical stage and the expression of ER, PR, and HER2 in primary untreated breast carcinoma. Methods: A retrospective immunohistochemical analysis of archived tissue blocks collected from 153 women, who underwent total mastectomy and lymph node dissection, included the expression of two hypoxia-related proteins: HIF-1α and GLUT1. Results: GLUT1 labelling index (LI) showed a positive correlation with T stage (R = 0.18, p = 0.026) and HER2 status (R = 0.25, p = 0.002), and a negative correlation with the expression of ER (R = −0.19, p = 0.017) and PR (R = −0.17, p = 0.032). HIF-1α LI showed a positive correlation with ER expression (R = 0.16, p = 0.045). In the multivariate regression analysis, a different relationship between classic prognostic factors and the two tested hypoxia proteins was proven. Higher GLUT1 expression correlated with ER and PR negativity (p = 0.02 and p = 0.01, respectively) as well as with higher expression of HER2 (p = 0.04). HIF-1α showed no association with PR and HER2, but a positive correlation with ER (p = 0.02). Neither of the hypoxia proteins was associated with a tumor grade. Only one clinical feature, T stage, correlated with both of the hypoxia markers: positively with GLUT1 (p = 0.049) and negatively with HIF-1α (p = 0.01) expression. Conclusions: In breast cancer, GLUT1 expression may be considered an additional prognostic factor which correlates with an adverse status of HER2 and hormonal receptors, and indicates a more hypoxic, radio- and chemotherapy refractory profile of carcinoma.

PL

Tło: Hipoksja w guzie nowotworowym stanowi niekorzystny czynnik prognostyczny, ogranicza jego promienioi chemiowrażliwość oraz promuje bardziej agresywny przebieg choroby. Przewidywanie rokowania i odpowiedzi na leczenie wymaga wiedzy o związku hipoksji z uznanymi czynnikami prognostycznymi. Celem badania było określenie zależności pomiędzy endogennymi markerami hipoksji w pierwotnym przewodowym raku piersi a klasycznymi czynnikami prognostycznymi, takimi jak stopień zaawansowania klinicznego oraz ekspresja receptorów ER, PR i HER2. Metody: Retrospektywna analiza immunohistochemiczna archiwizowanych bloczków tkanek pobranych od 153 kobiet, poddanych mastektomii i limfadenektomii pachowej, objęła ekspresję dwóch związanych z hipoksją białek: HIF-1α i GLUT1. Wyniki: Indeks wiązania GLUT1 (GLUT1 LI) wykazał korelację dodatnią z wielkością guza (R = 0,18, p = 0,026) i ekspresją HER2 (R = 0,25, p = 0,002) oraz ujemną z ekspresją ER (R = −0,19, p = 0,017) i PR (R = −0,17, p = 0,032). HIF-1α LI korelował wyłącznie z ekspresją ER (R = 0,16, p = 0,045). W analizie wieloczynnikowej wykazano zróżnicowaną zależność pomiędzy klasycznymi czynnikami prognostycznymi i testowanymi markerami hipoksji. GLUT1 LI korelował negatywnie z ekspresją ER i PR (odpowiednio p = 0,02 i p = 0,01) oraz pozytywnie z ekspresją HER2 (p = 0,04). Nie udowodniono korelacji pomiędzy HIF-1α LI a ekspresją PR czy HER2, natomiast wykazano jego dodatnią zależność z ekspresją ER (p = 0,02). Żaden marker hipoksji nie korelował ze stopniem zróżnicowania histologicznego nowotworu. Tylko jeden kliniczny czynnik – wielkość guza (T) – korelował z ekspresją badanych białek: dodatnio z GLUT1 (p = 0,049), a ujemnie z HIF-1α (p = 0,01). Wnioski: Ekspresja GLUT1 w raku piersi może stanowić dodatkowy czynnik prognostyczny, korelujący z niekorzystnym statusem receptora HER2 i receptorów hormonalnych oraz wskazywać na bardziej hipoksyczny, oporny na radioi chemioterapię, profil raka.

8

Changes Related to Fatigue in Cardiorespiratory Response Sensitivity to Hypoxic and Hypercapnic Stimulation during Strenuous Physical Load

88%

Mishchenko V., Suchanowski A., Lysenko O.

Baltic Journal of Health and Physical Activity

|

2009

|

vol. 1

|

issue 1

27-32

EN

Background: The aim was to study changes in the sensitivity of CRS responses of skilled athletes caused by fatigue during a strenuous physical load.Material/Methods: Response sensitivity to hypoxic and hypercapnic stimuli was analyzed in a group of high performance rowers (n=12) aged 18-22 years during exercising on "Concept-II" rowing ergometer. Two types of loads were used: sustained intensive load at high oxygen consumption (78-83% of VO2max) and relatively easier load (49-62% of VO2max) performed within 5 minutes. The method of rebreathing was used to determine responses sensitivity to CO2.Results: The results showed an increase in respiratory response sensitivity to hypoxia and a decrease in sensitivity to acidosis stimulus of respiration (CO2-H+) at the end of a strenuous load in presence of fatigue. Ventilatory response to hypoxic stimulus increased reliably before the end of work. At high intensity of loads during increment hypercapnia even in highly trained athletes the inhibition of ventilatory response has been notedConclusions: The data provide additional grounds for correction of fatigue by means of regulating the character and the intensity of physical loads in the process of endurance training. It has been shown that changes in sensitivity of CRS responses and other aspects of reactive features are of importance for special work capacity manifestations.

9

Expression and hypoxia-responsiveness of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 in mammary gland malignant cell lines

88%

Minchenko O. H., Opentanova I. L., Ogura T., Minchenko D. O., Komisarenko S. V., Caro J., Esumi H.

|

2005

|

vol. 52

|

issue 4

881-888

EN

Recently, we have shown that PFKFB4 gene which encodes the testis isoenzyme of PFKFB is also expressed in the prostate and hepatoma cancer cell lines. Here we have studied expression and hypoxic regulation of the testis isoenzyme of PFKFB4 in several malignant cell lines from a female organ - the mammary gland. Our studies clearly demonstrated that PFKFB4 mRNA is also expressed in mammary gland malignant cells (MCF-7 and T47D cell lines) in normoxic conditions and that hypoxia strongly induces it expression. To better understand the mechanism of hypoxic regulation of PFKFB4 gene expression, we used dimethyloxalylglycine, a specific inhibitor of HIF-1α hydroxylase enzymes, which strongly increases HIF-1α levels and mimics the effect of hypoxia. It was observed that PFKFB4 expression in the MCF7 and T47D cell lines was highly responsive to dimethyloxalylglycine, suggesting that the hypoxia responsiveness of PFKFB4 gene in these cell lines is regulated by HIF-1 proteins. Moreover, desferrioxamine and cobalt chloride, which mimic the effect of hypoxia by chelating or substituting for iron, had a similar stimulatory effect on the expression of PFKFB mRNA. In other mammary gland malignant cell lines (BT549, MDA-MB-468, and SKBR-3) hypoxia and hypoxia mimics also induced PFKFB4 mRNA, but to variable degrees. The hypoxic induction of PFKFB4 mRNA was equivalent to the expression of PFKFB3, Glut1, and VEGF, which are known HIF-1-dependent genes. Hypoxia and dimethyloxalylglycine increased the PFKFB4 protein levels in all cell lines studied except MDA-MB-468. Through site-specific mutagenesis in the 5'-flanking region of PFKFB4 gene the hypoxia response could be limited. Thus, this study provides evidence that PFKFB4 gene is also expressed in mammary gland cancer cells and strongly responds to hypoxia via an HIF-1α dependent mechanism. Moreover, the PFKFB4 and PFKFB3 gene expression in mammary gland cancer cells has also a significant role in the Warburg effect which is found in all malignant cells.

10

N-myc downstream regulated 1 gene and its place in the cellular machinery

88%

Kitowska A., Pawełczyk T.

|

2010

|

vol. 57

|

issue 1

15-21

EN

The exact function of the protein product of N-myc downstream regulated 1 gene (NDRG1) is unclear. Depending on the tissue type the NDRG1 protein is localized in the cytoplasm, nucleus, mitochondrion or membranes. Moreover, the expression of NDRG1 may be altered by several factors such as hypoxia, heavy metals, DNA damage, hormones, oncogene, and tumor-suppressor genes. A number of studies emphasize the role of NDRG1 in cancerogenesis. Presumably NDRG1 participates in angiogenesis, metastases, and mechanisms leading to anti-cancer drug resistance. This review summarizes current knowledge about the NDRG1 gene and the position of NDRG1 protein in the cellular machinery. The role of NDRG1 in cancer pathogenesis and its possible usefulness as a prognostic factor for patients with cancer is also discussed.

11

New benzimidazole derivatives with potential cytotoxic activity - study of their stability by RP-HPLC

88%

Błaszczak-Świątkiewicz K., Mirowski M., Kaplińska K., Kruszyński R., Trzęsowska-Kruszyńska A., Mikiciuk-Olasik E.

|

2012

|

vol. 59

|

issue 2

279-288

EN

Obtained benzimidazole derivatives, our next synthesized heterocyclic compounds, belong to a new group of chemical bondings with potential anticancer properties (Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2006, J Liguid Chrom Rel Tech 29: 2367-2385; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2008, Wiad Chem 62: 11-12, in Polish; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2011, J Liguid Chrom Rel Tech 34: 1901-1912). We used HPLC analysis to determine stability of these compounds in 0.2% DMSO (dimethyl sulfoxide). Optimisation of the chromatographic system and validation of the established analytical method were performed. Reversed phases (RP-18) and a 1:1 mixture of acetate buffer (pH 4.5) and acetonitrile as a mobile phase were used for all the analysed compounds at a flow rate 1.0 mL/min. The eluted compounds were monitored using a UV detector, the wavelength was specific for compounds 6 and 9 and compounds 7 and 10. The retention time was specific for all four compounds. The used method was found to have linearity in the concentration range of (0.1 mg/mL-0.1 μg/mL) with a correlation coefficient not less than r2=0.9995. Statistical validation of the method proved it to be a simple, highly precise and accurate way to determine the stability of benzimidazole derivatives in 0.2% DMSO. The recoveries of all four compounds examined were in the range 99.24-100.00%. The developed HPLC analysis revealed that the compounds studied remain homogeneous in 0.2% DMSO for up to 96 h and that the analysed N-oxide benzimidazole derivatives do not disintegrate into their analogues - benzimidazole derivatives. Compounds 8, 6 and 9 exhibit the best cytotoxic properties under normoxic conditions when tested against cells of human malignant melanoma WM 115.

12

Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers

75%

Bobarykina A. Y., Minchenko D. O., Opentanova I. L., Moenner M., Caro J., Esumi H., Minchenko O. H.

|

2006

|

vol. 53

|

issue 4

789-799

EN

Previously we have shown that hypoxia strongly induces the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and -4 (PFKFB-3 and PFKFB-4) genes in several cancer cell lines via a HIF-dependent mechanism. In this paper we studied the expression and hypoxic regulation of PFKFB-4 and PFKFB-3 mRNA as well as its correlation with HIF-1α, HIF-2α, VEGF and Glut1 mRNA expression in the pancreatic cancer cell line Panc1 and two gastric cancer cell lines MKN45 and NUGC3. This study clearly demonstrated that PFKFB-3 and PFKFB-4 mRNA are expresses in MKN45, NUGC3 and Panc1 cancers cells and that both genes are responsive to hypoxia in vitro. However, their basal level of expression and hypoxia responsiveness vary in the different cells studied. Particularly, PFKFB-3 mRNA is highly expressed in MKN45 and NUGC3 cancer cells, with the highest response to hypoxia in the NUGC3 cell line. The PFKFB-4 mRNA has a variable low basal level of expression in both gastric and pancreatic cancer cell lines. However, the highest hypoxia response of PFKFB-4 mRNA is found in the pancreatic cancer cell line Panc1. The basal level of PFKFB-4 protein expression is the highest in NUGC3 gastric cancer cell line and lowest in Panc1 cells, with the highest response to hypoxia in the pancreatic cancer cell line. Further studies showed that PFKFB-3 and PFKFB-4 gene expression was highly responsive to the hypoxia mimic dimethyloxalylglycine, a specific inhibitor of HIF-α hydroxylase enzymes, suggesting that the hypoxia responsiveness of PFKFB-3 and PFKFB-4 genes in these cell lines is regulated by the HIF transcription complex. The expression of VEGF and Glut1, which are known HIF-dependent genes, is also strongly induced under hypoxic conditions in gastric and pancreatic cancer cell lines. The levels of HIF-1α protein are increased in both gastric and pancreatic cancer cell lines under hypoxic conditions. However, the basal level of HIF-1α as well as HIF-2α mRNA expression and their hypoxia responsiveness are different in the MKN45 and NUGC3 cancer cells. Thus, the expression of HIF-1α mRNA is decreased in both gastric cancer cell lines treated by hypoxia or dimethyloxalylglycine, but HIF-2α mRNA expression is not changed significantly in NUGC3 and slightly increased in MKN45 cells. Expression of PFKFB-4 and PFKFB-3 was also studied in gastric cancers and corresponding nonmalignant tissue counterparts from the same patients on both the mRNA and protein levels. The expression of PFKFB-3 and PFKFB-4 mRNA as well as PFKFB-1 and PFKFB-2 mRNA was observed in normal human gastric tissue and was increased in malignant gastric tumors. The basal level of PFKFB-4 protein expression in gastric cancers was much higher as compared to the PFKFB-3 isoenzyme. In conclusion, this study provides evidence that PFKFB-4 and PFKFB-3 genes are also expressed in gastric and pancreatic cancer cells, they strongly respond to hypoxia via a HIF-1α dependent mechanism and, together with the expression of PFKFB-1 and PFKFB-2 genes, possibly have a significant role in the Warburg effect which is found in malignant cells.

13

In vitro reoxygenation following hypoxia increases MMP-2 and TIMP-2 secretion by human umbilical vein endothelial cells

75%

Cavdar Z., Oktay G., Egrilmez M., Genc S., Genc K., Altun Z., Islekel H., Guner G.

|

2010

|

vol. 57

|

issue 1

69-73

EN

Endothelial cells lining the inner blood vessel walls play a key role in the response to hypoxia, which is frequently encountered in clinical conditions such as myocardial infarction, renal ischemia and cerebral ischemia. In the present study we investigated the effects of hypoxia and hypoxia/reoxygenation on gelatinases (matrix metalloproteinase-2 and -9), their inhibitor (TIMP-2) and activator (MT1-MMP), in human umbilical vein endothelial (HUVE) cells. HUVE cells were subjected to 4 h of hypoxia or hypoxia followed by 4 and 24 h of reoxygenation. The pro- and active forms of MMP-2 and MMP-9 were analyzed by gelatin zymography; TIMP-2 protein level was assayed using ELISA, while MT1-MMP activity was measured using an activity assay. The secretion of MMP-2 proform increased significantly in cells subjected to 4 h of hypoxia followed by 4 or 24 h of reoxygenation, compared with the normoxic group. TIMP-2 protein level also increased significantly in the hypoxia/reoxygenation groups, compared with the normoxic group. There were no statistically significant differences in the levels of active MT1-MMP in all groups. This study indicates that MMP-2 and TIMP-2 could be regarded as important components of a mechanism in the pathophysiology of ischemic injury following reperfusion.

14

Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis.

75%

Kimura H., Esumi H.

|

2003

|

vol. 50

|

issue 1

49-59

EN

Physiologically, angiogenesis is tightly regulated, or otherwise it leads to pathological processes, such as tumors, inflammatory diseases, gynecological diseases and diabetic retinopathy. The vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis. The VEGF gene expression is regulated by a variety of stimuli. Hypoxia is one of the most potent inducers of the VEGF expression. The hypoxia inducible factor 1 (HIF-1) plays as a key transcription factor in hypoxia-mediated VEGF gene upregulation. Nitric oxide (NO) as well as hypoxia is reported to upregulate the VEGF gene by enhancing HIF-1 activity. The Akt/protein kinase B (PKB) pathway may be involved in NO-mediated HIF-1 activation in limited cell lines. There are some reports of negative effects of NO on HIF-1 and VEGF activity. These conflicting data of NO effects may be attributed mainly to the amount of released NO. Indeed, NO can be a positive or negative modulator of the VEGF gene under the same conditions simply by changing its amounts. The VEGF-mediated angiogenesis requires NO production from activated endothelial NO synthase (eNOS). Activation of eNOS by VEGF involves several pathways including Akt/PKB, Ca2+/calmodulin, and protein kinase C. The NO-mediated VEGF expression can be regulated by HIF-1 and heme oxygenase 1 (HO-1) activity, and the VEGF-mediated NO production by eNOS can be also modulated by HIF-1 and HO-1 activity, depending upon the amount of produced NO. These reciprocal relations between NO and VEGF may contribute to regulated angiogenesis in normal tissues.

15

Antiproliferative activity of new benzimidazole derivatives

75%

Błaszczak-Świątkiewicz K., Olszewska P., Mikiciuk-Olasik E.

|

2013

|

vol. 60

|

issue 3

427-433

EN

A series of new benzimidazole derivatives were synthesized and tested in vitro for possible anticancer activity. Their effect of proliferation into selected tumor cell lines at normoxia and hypoxia conditions was determined by WST-1 test. Additionally, apoptosis test (caspase 3/7 assay) was used to check the mode caused by the agents of cell death. Four of the examined compounds (7, 8, 13, 11) showed a very good antiproliferative effect and three of them were specific for hypoxia conditions (8, 14, 11). Compound 8 was the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/ normoxia cytotoxic coefficient of compound 14 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) - a reference compound in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Screening test of caspase-dependent apoptosis proved that exposure to A549 cells of compounds 7-8 and 13-14 for 48 h promote apoptotic cell death. These results supplement our earlier study of the activity of new potentialy cytotoxic heterocyclic compounds against selected tumor cells.

16

Specifics of Ventilatory and Heart Rate Chemosensitivity Related to Special Endurance Capacity in High Performance Alpinists and Endurance Athletes

75%

Mishchenko V., Pavlik A., Suchanowski A.

Baltic Journal of Health and Physical Activity

|

2009

|

vol. 1

|

issue 2

97-104

EN

Background: The aim was to compare ventilatory and heart rate chemosensitivity to hypoxia and hypercapnia in homogenous groups of high performance alpinists and endurance athletes and its relation to special work endurance.Material/Methods: Thirty-two male best national alpinists (30.7±2.7 yrs, VO2max 63.7±1.9 ml. kg-1,min-1, 14.3±2.4 yrs of experience) and 24 high performance male road cyclists of national team (25.7±1.1 yrs, VO2max 74.5±1.5 ml.kg-1,min-1, 11.2±1.4 yrs of experience) were examined by isocapnic progressive hypoxia and CO2 rebreathing tests. Maximal oxygen uptake, lung ventilation and heart rate peak responses were measured in an incremental ergometric test at sea level. Special work capacity of 23 alpinists was evaluated as the best time of non complicated mountain climbing between the point at 3,290 and 4,300 m above the sea level. Special work capacity of cyclists was evaluated as the best time of the individual 50 km race at the sea level.Results: The results showed no significant differences of the hypoxic ventilatory response in groups of alpinists and cyclists (p<0.05) But circulatory response evaluated by response of HR increase in answer to a decrease in O2 arterial blood saturation (SaO2) in alpinists was lower (p<0.05). Results showed that the evaluation of ventilatory and heart rate chemosensitivity in addition to measure of aerobic power may give important information for prevision of specific working capacity of high performance alpinists. Maximal oxygen uptake (ml/kg body mass) of the four best alpinists did not differ from the values of other alpinists. Special work capacity of alpinists was significantly related to tidal volume increase for the hypoxia test (r=-0.60) and to CO2 sensitivity (r=-0.67).Conclusions: The long-term exposure to environmental hypoxia and hypocapnia in alpinists generates specific changes in respiratory control. To evaluate special work capacity potential possibilities in a homogenous group of high performance alpinists first of all heart rate response sensitivity to hypoxia as well ventilatory response sensitivity to CO2 had to be taken into account, but only an alpinist's aerobic power.

17

Niedotlenienie guza jako czynnik predykcyjny w radioterapii onkologicznej

63%

Martenka P., Roszak A.

Ginekologia Onkologiczna

|

2006

|

vol. 4

|

issue 2

99-107

EN

Radiotherapy is, next to surgery, the basic method of treatment in oncology. The intensive searching of the predictive factors for radiotherapy effectiveness, are still continuing. The mechanism of radiotherapy action depends on the cellular oxygen presence. The latest studies evidence, that the molecular oxygen, through the mechanism of fixation, leads to destruction of the DNA damage, caused by the ionizing radiation, repair. Number of studies has demonstrated, that the tumour hypoxia evaluation correlates with radiotherapy effectiveness. However, the universal method assessing the tumour hypoxia does not exist. Actually used methods, as Eppendorf’s electrode, the molecular markers of hypoxia evaluation, or PET studies with oxydo-reductive radiopharmaceutical agents, bring conflicting results. So, a lot of doubts about the quantitative and qualitative character of relationship between hypoxia and sensitivity for radiotherapy still exist. Moreover, the analysis is impeded by fact, that the hypoxia has significant negative prognostic influence on the treatment results with radiotherapy, through the genome and proteomic changes induction. The paper presents the actual status of knowledge about the influence of tumour hypoxia on radiotherapy effectiveness.

PL

Radioterapia jest obok chirurgii podstawową metodą leczenia nowotworów. Trwają obecnie intensywne poszukiwania czynników predykcyjnych dla skuteczności radioterapii. Mechanizm działania radioterapii zależny jest od obecności tlenu w komórce. Najnowsze doświadczenia dowodzą, że tlen cząsteczkowy poprzez mechanizm fiksacji zaburza naprawę uszkodzeń wywołanych w DNA promieniowaniem jonizującym. Liczne badania wykazały, że ocena niedotlenienia guza koreluje z wynikiem radioterapii. Brak jednak uniwersalnej metody oceniającej hipoksję. Aktualnie stosowane metody, jak pomiar elektrodą Eppendorfa, ocena markerów molekularnych hipoksji czy badania PET z użyciem oksydoredukcyjnych radiofarmaceutyków dostarczają sprzecznych wyników. Istnieje więc wiele wątpliwości co do ilościowego i jakościowego charakteru zależności między niedotlenieniem a wrażliwością na radioterapię. Ponadto analizę utrudnia fakt, że niedotlenienie wywiera znaczny negatywny prognostyczny wpływ na wyniki leczenia radioterapią poprzez indukcję zmian genomowych i proteomicznych. W pracy przedstawiono aktualny stan wiedzy na temat wpływu niedotlenienia guza na skuteczność radioterapii.

18

Zjawiska autoskopiczne – przegląd badań i opis przypadku

63%

Pawełczyk A., Żurner-Szymańska N., Pawełczyk T., Rabe-Jabłońska J.

|

issue 3

193-198

EN

Autoscopic phenomena are defined as seeing one’s body in space, from internal perspective (as in a mirror) or from external point of view. They have different pictures, therefore they have been presently classified to the groups of: “being out of the body”, heautoscopy, and autoscopic hallucinations. “Being out of the body” is defined as an impression of seeing the world and one’s own body at a distance, from an enhanced visual-spatial perspective, autoscopic hallucinations are described as seeing one’s double in space out of one’s body but without a sense of having left the body, and heautoscopy – as seeing oneself in space out of one’s body but with difficulty in specifying where “experiencing of one’s self” and “one’s own centre of awareness” are located. The analysis of neurophysiological andneuroimaging data associated with experiencing autoscopy implies the presence of disturbances in integration of information flowing from the atrial system and other receptors (visual, proprioceptive, and tactile receptors). Neuroimaging studies indicated also participation of prefrontal, parietal and temporal cortices associated with a higher level of processing the information about oneself. These deficits are most probably associated with damages in temporoparietal junctions and in neuronal junction networks in various regions of the cerebral cortex, including prefrontal, parietal and temporal regions. Apart from the review of literature, the article presents a case of the patient who had the central nervous system’s hypoxia due to haemorrhagic shock. Because of his cerebral hypoxia the patient exhibited heautoscopic sensations and was close to death. The authors describe his experiences containing many elements repeated in accounts of people in a similar somatic condition. The final part of the article presents possible causes of their occurrence.

PL

Zjawiska autoskopiczne definiowane są jako spostrzeganie własnego ciała w przestrzeni, z perspektywy wewnętrznej (tak jak w lustrze) lub z zewnętrznego punktu widzenia. Mają one różny obraz i w związku z nim zostały obecnie zaklasyfikowane do grup: „bycia poza ciałem”, heautoskopii i halucynacji autoskopicznych. „Bycie poza ciałem” definiowane jest jako wrażenie widzenia świata i własnego ciała z odległości, z podwyższonej wzrokowo-przestrzennej perspektywy, autoskopiczne halucynacje opisuje się jako widzenie swojego sobowtóra w przestrzeni poza własnym ciałem, lecz bez odczucia opuszczenia ciała, a heautoskopię – jako widzenie siebie w przestrzeni poza własnym ciałem, ale z trudnościami w określeniu, gdzie jest zlokalizowane „poczucie siebie” i „własne centrum świadomości”. Analiza danych neurofizjologicznych i neuroobrazowych związanych z doświadczeniem autoskopii sugeruje obecność zakłóceń integracji informacji płynących z układu przedsionkowego i innych receptorów (wzrokowych, proprioceptywnych, dotykowych). W badaniach neuroobrazowych wykazano udział w tych procesach także kory przedczołowej, ciemieniowej i skroniowej, związanych z wyższym poziomem przetwarzania informacji o samym sobie. Deficyty te najprawdopodobniej wiążą się z uszkodzeniami w połączeniach ciemieniowo-skroniowych oraz w sieciach połączeń neuronalnych różnych okolic kory mózgu, w tym przedczołowej, ciemieniowej i skroniowej. W artykule oprócz przeglądu literatury zaprezentowano przypadek pacjenta, u którego w następstwie wstrząsu krwotocznego doszło do hipoksji w ośrodkowym układzie nerwowym. W wyniku niedotlenienia mózgu pacjent przeżył stan bliski śmierci i miał doznania heautoskopiczne. Autorzy przedstawiają opisy jego doświadczeń, zawierające wiele elementów powtarzających się w relacjach osób w podobnym stanie somatycznym. W końcowej części artykułu omówiono możliwe podłoże ich pojawienia się.

19

Ruchy mimowolne po przebytym udarze mózgu u pacjenta z przewlekłą niewydolnością oddechową

63%

Baszkiewicz M.

Aktualności Neurologiczne

|

2014

|

vol. 14

|

issue 1

30-33

EN

Introduction: Movement disorders in the form of involuntary movements are a rare complication of stroke, found in approximately 4% of patients. Material and methods: This case is presented on the basis of medical records of the patient. Case study: This paper presents the case of a 73-year-old patient with chronic obstructive pulmonary disease, a history of an ischaemic stroke, who was treated repeatedly at the Department of Neurology due to poststroke involuntary movements involving the left upper extremity, head and tongue. Computed tomography of the head revealed: bilateral vascular focal lesions in the projection of basal ganglia. Frequently, the decrease in oxygen saturation (SpO2) levels below 90% was observed in the patient, when involuntary movements intensified. When the patient was saturated with oxygen, involuntary movements were remitted, and reappeared after some time but their amplitude was significantly narrower. Involuntary movements completely regressed after new cerebral ischaemic accidents in the right frontal lobe. Results and discussion: Chorea-ballism and dystonic movements are associated with damage to the basal ganglia, most commonly developed as a result of lesions of a vascular origin. In the case of our patient, vascular lesions were confirmed by a computed tomography scan. Conclusions: In the presented case massive involuntary movements intensified when saturation levels dropped below 90%. This can be associated with the adverse effect of hypoxia in focal ischaemia involving the brain. Remission of involuntary movements may have been caused by the development of a new ischaemic lesion in the right frontal lobe.

PL

Wstęp: Ruchy mimowolne są rzadkim objawem udaru mózgu, występującym u około 4% chorych. Materiał i metoda: Przypadek przedstawiono na podstawie dokumentacji medycznej pacjenta. Opis przypadku: Raport opisuje przypadek 73-letniego pacjenta z przewlekłą obturacyjną chorobą płuc i po niedokrwiennym udarze mózgu. Chory był kilkukrotnie leczonego na Oddziale Neurologii z powodu ruchów mimowolnych lewej kończyny górnej, głowy i języka. W tomografii komputerowej głowy w rzucie jąder podstawy stwierdzono obustronnie ogniska naczyniopochodne. U pacjenta wiele razy obserwowano spadek saturacji tlenem poniżej 90%, co znacznie nasilało ruchy mimowolne. Po nasyceniu tlenem ruchy te ustępowały, by pojawić się po jakimś czasie, ale już ze znacznie mniejszą amplitudą. Po udarze niedokrwiennym w prawej okolicy czołowej ruchy mimowolne zanikły samoistnie. Wyniki: Ruchy balistyczno-pląsawicze i dystoniczne są związane z uszkodzeniem jąder podkorowych, najczęściej w przebiegu zmian naczyniopochodnych. U opisywanego pacjenta zmiany naczyniopochodne zostały potwierdzone w badaniu tomograficznym. Wnioski: W przedstawionym przypadku masywne ruchy mimowolne nasilały się przy spadku saturacji tlenem poniżej 90%, co można wiązać z niekorzystnym działaniem hipoksji na obszary niedokrwienne mózgowia. Przyczyną ustąpienia ruchów mimowolnych mogło być powstanie nowego ogniska niedokrwiennego w prawym płacie czołowym i zahamowanie działania pobudzającego jąder podstawy na układ ruchowy.

20

Inhibition of IRE1 signaling affects expression of a subset genes encoding for TNF-related factors and receptors and modifies their hypoxic regulation in U87 glioma cells

51%

Minchenko O. H., Kryvdiuk I. V., Minchenko D. O., Riabovol O. O., Halkin O. V.

Endoplasmic Reticulum Stress in Diseases

|

2016

|

vol. 3

|

issue 1

EN

Inhibition of IRE1 (inositol requiring enzyme-1), the major signaling pathway of endoplasmic reticulum stress, significantly decreases tumor growth and proliferation of glioma cells. To elucidate the role of IRE1- mediated glioma growth, we studied the expression of a subset genes encoding for TNF (tumor necrosis factor)- related factors and receptors and their hypoxic regulation in U87 glioma cells overexpressing dominant-negative IRE1 (dnIRE1). We demonstrated that the expression of TNFAIP1, TNFRSF10D, TNFRSF21, TNFRSF11B, TNFSF7, and LITAF genes is increased in glioma cells with modified IRE1; however, TNFRSF10B, TRADD, and TNFAIP3 is down-regulated in these cells as compared to their control counterparts. We did not find TNFRSF1A gene expression to change significantly under this experimental condition. In control glioma cells, hypoxia leads to the up-regulated expression of TNFAIP1, TNFAIP3, TRADD, and TNFRSF10D genes and the concomitant down-regulation of TNFRSF21, TNFRSF11B, and LITAF genes; while, TNFRSF10B and TNFRSF1A genes are resistant to hypoxic treatment. However, inhibition of IRE1 modifies the hypoxic regulation of LITAF, TNFRSF21, TNFRSF11B, and TRADD genes and introduces hypoxia-induced sensitivity to TNFRSF10B, TNFRSF1A, and TNFSF7 gene expressions. Furthermore, knockdown by siRNA of TNFRSF21 mRNA modifies the hypoxic effect on the IRE1-dependent rate of proliferation and cell death in U87 glioma cells. The present study demonstrates that fine-tuned manipulation of the expression of TNF-related factors and receptors directly relating to cell death and proliferation, is mediated by an effector of endoplasmic reticulum stress, IRE1, as well as by hypoxia in a gene-specific manner. Thus, inhibition of the kinase and endoribonuclease activities of IRE1 correlates with deregulation of TNF-related factors and receptors in a manner that is gene specific and thus slows tumor growth.

Refine search results

The direction of the changes of rates of the internal and external training load under the influence of high-altitude hypoxia on mountain bikers

Properties of B16-F10 murine melanoma cells subjected to metabolic stress conditions

An Assessment of Exercise Tolerance in Normobaric Hypoxia of Patients with Diabetes Mellitus Type 1

Influence of Hypoxia Training on the Aerobic Capacity of an Elite Race Walker

Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin

Altitude Training and its Influence on Physical Endurance in Swimmers

Differential relationship between two hypoxia markers: HIF-1α and GLUT1 and classic prognostic factors in invasive breast carcinoma

Changes Related to Fatigue in Cardiorespiratory Response Sensitivity to Hypoxic and Hypercapnic Stimulation during Strenuous Physical Load

Expression and hypoxia-responsiveness of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 in mammary gland malignant cell lines

N-myc downstream regulated 1 gene and its place in the cellular machinery

New benzimidazole derivatives with potential cytotoxic activity - study of their stability by RP-HPLC

Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers

In vitro reoxygenation following hypoxia increases MMP-2 and TIMP-2 secretion by human umbilical vein endothelial cells

Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis.

Antiproliferative activity of new benzimidazole derivatives

Specifics of Ventilatory and Heart Rate Chemosensitivity Related to Special Endurance Capacity in High Performance Alpinists and Endurance Athletes

Niedotlenienie guza jako czynnik predykcyjny w radioterapii onkologicznej

Zjawiska autoskopiczne – przegląd badań i opis przypadku

Ruchy mimowolne po przebytym udarze mózgu u pacjenta z przewlekłą niewydolnością oddechową

Inhibition of IRE1 signaling affects expression of a subset genes encoding for TNF-related factors and receptors and modifies their hypoxic regulation in U87 glioma cells